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Albert Chan

Publications and source records attributed to Albert Chan.

13 recordsLinked to original sources
PubMed2006

PIPE: a protein-protein interaction prediction engine based on the re-occurring short polypeptide sequences between known interacting protein pairs.

BACKGROUND: Identification of protein interaction networks has received considerable attention in the post-genomic era. The currently available biochemical approaches used to detect protein-protein interactions are all time and labour intensive. Consequently there is a growing need for the development of computational tools that are capable of effectively identifying such interactions. RESULTS: Here we explain the development and implementation of a novel Protein-Protein Interaction Prediction Engine termed PIPE. This tool is capable of predicting protein-protein interactions for any target pair of the yeast Saccharomyces cerevisiae proteins from their primary structure and without the need for any additional information or predictions about the proteins. PIPE showed a sensitivity of 61% for detecting any yeast protein interaction with 89% specificity and an overall accuracy of 75%. This rate of success is comparable to those associated with the most commonly used biochemical techniques. Using PIPE, we identified a novel interaction between YGL227W (vid30) and YMR135C (gid8) yeast proteins. This lead us to the identification of a novel yeast complex that here we term vid30 complex (vid30c). The observed interaction was confirmed by tandem affinity purification (TAP tag), verifying the ability of PIPE to predict novel protein-protein interactions. We then used PIPE analysis to investigate the internal architecture of vid30c. It appeared from PIPE analysis that vid30c may consist of a core and a secondary component. Generation of yeast gene deletion strains combined with TAP tagging analysis indicated that the deletion of a member of the core component interfered with the formation of vid30c, however, deletion of a member of the secondary component had little effect (if any) on the formation of vid30c. Also, PIPE can be used to analyse yeast proteins for which TAP tagging fails, thereby allowing us to predict protein interactions that are not included in genome-wide yeast TAP tagging projects. CONCLUSION: PIPE analysis can predict yeast protein-protein interactions. Also, PIPE analysis can be used to study the internal architecture of yeast protein complexes. The data also suggests that a finite set of short polypeptide signals seem to be responsible for the majority of the yeast protein-protein interactions.

Algorithms↗
PubMed2006

Retinal vascular caliber and risk of retinopathy in young patients with type 1 diabetes.

OBJECTIVE: To examine the relationship between retinal vascular caliber and incident retinopathy in children and adolescents with type 1 diabetes mellitus. DESIGN: Hospital-based case-control study with prospective outcomes. PARTICIPANTS: Cases and controls were selected from a cohort of children and adolescents 12 to 20 years old with type 1 diabetes followed up at a tertiary diabetes clinic. Cases were patients who developed incident diabetic retinopathy (n = 166) after at least 1 year of follow-up (> or =2 clinic visits), and controls were patients who had not developed retinopathy (n = 165) after > or =2 years of follow-up (> or =3 clinic visits). Baseline retinal photographs of cases and controls were digitized, and retinal vascular calibers were measured using a computer-assisted program by a grader masked to case-control status. These measurements were combined into summary indices reflecting the average arteriolar and venular calibers. MAIN OUTCOME MEASURE: Development of diabetic retinopathy. RESULTS: Incident retinopathy cases had retinal arteriolar calibers (mean +/- standard deviation [SD], 206.5+/-18.4 microm) significantly larger than those of controls (200.2+/-16.5 microm) (P = 0.004) but similar retinal venular calibers (329.1+/-14.7 microm in cases vs. 326.4+/-15.1 microm in controls, P = 0.312). After adjusting for age, gender, diabetes duration, glycated hemoglobin levels, blood pressure, body mass index, and pubertal stage, larger arteriolar caliber was predictive of risk of diabetic retinopathy (odds ratio, 1.44 per SD increase in arteriolar caliber; 95% confidence interval, 1.11-1.86). CONCLUSION: Larger retinal arteriolar caliber predicts incident retinopathy in children and adolescents with type 1 diabetes, independent of conventional risk factors for retinopathy. Measurement of retinal vascular caliber may provide prognostic information regarding the subsequent risk of diabetic retinopathy.

Adolescent↗
PubMed2006

Marked differences in the structures and protein associations of lymphocyte and monocyte CD4: resolution of a novel CD4 isoform.

The structures, molecular interactions and functions of CD4 in a subset of T lymphocytes have been well characterized. The CD4 receptors of other cell types have, however, been poorly documented. We have previously shown that lymphocytes and monocytes/macrophages differ in their expression of CD4 monomers and dimers. In the present study, we have shown further significant differences. Variability in the blocking of CD4 mAb binding by sulfated polyanions indicated differences in exofacial CD4 structures. In contrast to the well-documented 55 kDa monomers in lymphocytic cells, monocytic cells were found to coexpress two monomer isoforms: the 55 kDa form and a novel 59 kDa species. Experimental uncoupling of CD4 disulfides indicated that the oxidized 55 kDa monomer could be converted to the 59 kDa form. This was achieved by chemical reduction of purified native or recombinant CD4, or in cell transfection experiments by mutation of cysteine to alanine in domain 1 (D1) (Cys16 or Cys84) and in domain 4 (D4) (Cys303 or Cys345). All of these modifications promote CD4 distension on SDS-PAGE analysis and indicate that, when CD4 inter-beta-sheet disulfides in the D1 and D4 Ig folds are disrupted, there is an unravelling of the oxidized form to an extended 59 kDa unfolded state. We hypothesize that this may be a transition-state, structural-intermediate in the formation of disulfide-linked homodimers. Also identified were CD4-tyrosine kinase dissimilarities in which lymphocyte CD4 associated with Lck, but monocyte CD4 associated with HcK. These findings show that there is complex heterogeneity in structures and interactions in the CD4 of T lymphocytes and monocytes.

Amino Acid Substitution↗
PubMed2005

Accurate prediction of HIV-1 drug response from the reverse transcriptase and protease amino acid sequences using sparse models created by convex optimization.

MOTIVATION: Genotype-phenotype modeling problems are often overcomplete, or ill-posed, since the number of potential predictors-genes, proteins, mutations and their interactions-is large relative to the number of measured outcomes. Such datasets can still be used to train sparse parameter models that generalize accurately, by exerting a principle similar to Occam's Razor: When many possible theories can explain the observations, the most simple is most likely to be correct. We apply this philosophy to modeling the drug response of Type-1 Human Immunodeficiency Virus (HIV-1). Owing to the decreasing expense of genetic sequencing relative to in vitro phenotype testing, a statistical model that reliably predicts viral drug response from genetic data is an important tool in the selection of antiretroviral therapy (ART). The optimization techniques described will have application to many genotype-phenotype modeling problems for the purpose of enhancing clinical decisions. RESULTS: We describe two regression techniques for predicting viral phenotype in response to ART from genetic sequence data. Both techniques employ convex optimization for the continuous subset selection of a sparse set of model parameters. The first technique, the least absolute shrinkage and selection operator, uses the l(1) norm loss function to create a sparse linear model; the second, the support vector machine with radial basis kernel functions, uses the epsilon-insensitive loss function to create a sparse non-linear model. The techniques are applied to predict the response of the HIV-1 virus to 10 reverse transcriptase inhibitor and 7 protease inhibitor drugs. The genetic data are derived from the HIV coding sequences for the reverse transcriptase and protease enzymes. When tested by cross-validation with actual laboratory measurements, these models predict drug response phenotype more accurately than models previously discussed in the literature, and other canonical techniques described here. Key features of the methods that enable this performance are the tendency to generate simple models where many of the parameters are zero, and the convexity of the cost function, which assures that we can find model parameters to globally minimize the cost function for a particular training dataset. AVAILABILITY: Results, tables and figures are available at ftp://ftp.genesecurity.net. SUPPLEMENTARY INFORMATION: An Appendix to accompany this article is available at Bioinformatics online.

Amino Acid Sequence↗
PubMed2005

Detection of Herba Aristolochia Mollissemae in a patient with unexplained nephropathy.

The authors report a case of unexplained nephropathy 2 months after ingestion of Herba Aristolochia Mollissemae in a patient with long-standing Crohn's disease and recently diagnosed carcinoma of the colon. It presented as a relentlessly progressing hypocellular interstitial nephritis 5 months after cessation of an earlier course of mesalazine. The patient finally had end-stage renal failure 12 months after taking herbs and required hemodialysis. Aristolochic acid (AA) was detected in the herbal sample of Herba Aristolochia Mollissemae by high-performance liquid chromatography-diode array detection and electrospray ionization-tandem mass spectrometry. Specific AA-DNA adducts were detected in the renal biopsy by 32 P-postlabelling analysis. Transitional cell carcinoma was diagnosed 5 months after herb ingestion. It was found that the originally prescribed nonnephrotoxic herb had been substituted by AA-containing Herba Aristolochia Mollissemae at the wholesaler level. Although AA-associated nephropathy could not be proved conclusively, the current case contributed to the withdrawal of the AA-related herbs by the local health authority in Hong Kong. Physicians should be on the alert for herbal nephrotoxicity by possible replacement of nontoxic herbs by nephrotoxic herbs.

Aristolochiaceae↗
PubMed2005

The case for biennial retinopathy screening in children and adolescents.

OBJECTIVE: Current guidelines recommend annual retinopathy screening 2 years after onset (for pubertal-onset type 1 diabetes) and after 5 years (or age 11, whichever is earlier) for prepubertal onset. Our aim was to describe the natural history of retinopathy and to explore optimal retinal screening intervals for children and adolescents (aged <20 years) screened according to these guidelines. RESEARCH DESIGN AND METHODS: More than 1,000 children and adolescents, followed longitudinally, were screened for retinopathy using seven-field stereoscopic fundus photography through dilated pupils. Of these, 668 had baseline and follow-up retinal screening. Using generalized estimating equations, we compared the risk of retinopathy with baselines at yearly intervals, in older and younger groups, in higher risk groups (diabetes duration >10 years or HbA(1c) >10% at any screening), and after stratification </=10 and <10 years in duration. RESULTS: After 1 year, retinopathy did not increase significantly in the older group (n = 618, median HbA(1c) 8.7%, range 8.0-9.5), younger group (n = 50, median HbA(1c) 8.5%, range 8.0-9.2), or the higher-risk groups. Retinopathy increased significantly after 2 years in the older group (P = 0.003) but not until 6 years in the younger group (P = 0.01). In the group with HbA(1c) >10% recorded at any visit, retinopathy increased significantly after 2 years (P = 0.001) but not until 3 years in the group whose HbA(1c) was always </=10% (P = 0.003). After the second eye assessment, retinopathy did not increase significantly until 3 and 6 years later in the older and younger groups, respectively (P = 0.028 and 0.014). CONCLUSIONS: These results suggest that adolescents (in reasonable metabolic control) could safely be screened every 2 years rather than the currently recommended 1-year interval. In younger children, the next screening interval could be >2 years later. Individuals with especially poor control, duration >10 years, or significant retinopathy should be screened more frequently.

Adolescent↗
PubMed2004

House dust mite allergen (Derp1 and Blot5) levels in asthmatics' home in Hongkong.

OBJECTIVE: To measure Derp1 and Blot5 allergen levels in asthmatics' homes in Hongkong. METHODS: Seventy houses were enrolled for a mite indoor environment study. Dust samples were obtained from two sites of each patients' house: bed and floor. Derp1 and Blot5 levels were quantified by a two-site monoclonal antibody-based ELISA technique. RESULTS: The levels of Derp1 allergens found in bed (geometric mean (GM) 3.43 microg/g of dust; 95%CI, 1.89-4.96 microg/g) and on the floor (GM 1.12 microg/g of dust; 95%CI, 0.71-1.53 microg/g) indicated significant differences (P=0.005). However, the levels of Blot5 allergens found in bed (GM 19.00 microg/g of dust; 95%CI, 0.89-38.90 microg/g) and on the floor (GM 6.14 microg/g of dust; 95%CI, 0.40-11.90 microg/g) showed no statistically significant difference. In addition, in regards to the exposure index for Derp1 and Blot5 allergens found in bed and on the floor, 17.6% in bed and 8.6% on the floor had levels of Blot5 > or = 10 microg/g of dust, higher than those obtained for Derp1 (7.2% and 0% in bed and on the floor respectively, P<0.05); higher percentages in bed and on the floor (25.0% and 35.7%) were observed for levels of Blot5 = 0 microg/g of dust as compared with Derp1 in bed and on the floor (4.3% and 14.5% respectively, P<0.05). CONCLUSIONS: Derp1 and Blot5 are the major allergens found in this regional study, Blot5 is a more potent allergen in Hongkong, probably reflecting the high level of exposure to Blomia tropicalis (Bt). Bt and Dermatophagoides pteronyssinus (Dp) allergens should be included for precise diagnosis and effective immuno-therapeutic treatment of mite allergy in Hongkong.

Allergens↗
PubMed2002

Death following creatine kinase-MB elevation after coronary intervention: identification of an early risk period: importance of creatine kinase-MB level, completeness of revascularization, ventricular function, and probable benefit of statin therapy.

BACKGROUND: Creatine kinase (CK)-MB elevation after percutaneous coronary intervention (PCI) has been associated with subsequent cardiac death. The patients at risk, the timing of risk, and potential treatment implications are uncertain. METHODS AND RESULTS: Eight thousand, four hundred nine consecutive non- acute myocardial infarction patients with successful PCI and no emergency surgery or Q-wave myocardial infarction were followed for 38+/-25 months; 1446 (17.2%) had post-PCI CK-MB above normal on routine ascertainment. Patients were prospectively stratified into those with CK-MB 1 to 5x or CK-MB >5x normal. No patient with CK-MB 1 to 5x normal died during the first week after PCI, and excess risk of early death for patients with CK-MB elevation occurred primarily in the first 3 to 4 months. The actuarial 4-month risk of death was 8.9%, 1.9%, and 1.2% for patients with CK-MB >5x, CK-MB 1 to 5x, and CK-MB < or =1x normal (P<0.001). Death within 4 months was independently correlated with the degree of CK-MB elevation, creatinine > or =2 mg%, post-PCI C-reactive protein, low ejection fraction, age, and congestive heart failure class (P<0.01 for all). In a matched subset analysis, incomplete revascularization (P<0.001), congestive heart failure class (P=0.005), and no statin treatment at hospital discharge (P=0.009) were associated with death. CONCLUSIONS: Patients with CK-MB elevation after PCI are at excess risk of death for 3 to 4 months, although prolonging hospitalization for CK-MB 1 to 5x is unlikely to modify risk. CK-MB >5x normal, incomplete revascularization, elevated C-reactive protein, heart failure, the elderly, and hospital discharge without on statin therapy increases risk. Several of these factors suggest that inflammation may play a part in the excess risk of death.

Aged↗
PubMed2002

Predictors of glycaemic control and hypoglycaemia in children and adolescents with type 1 diabetes from NSW and the ACT.

OBJECTIVES: To audit glycaemic control and incidence of severe hypoglycaemia in children and adolescents with type 1 diabetes in New South Wales (NSW) and the Australian Capital Territory (ACT). DESIGN: A multicentre, population-based, cross-sectional study from 1 September to 31 December, 1999. PARTICIPANTS: 1190 children and adolescents aged 1.2-15.8 years with type 1 diabetes, identified from three hospital-based paediatric diabetes units, four private city-based paediatric practices and 18 regional outreach clinics in NSW and the ACT. MAIN OUTCOME MEASURES: HbA(1c) level and incidence of severe hypoglycaemia (defined by unconsciousness or seizures). RESULTS: The response rate was 67% (1190 of a target group of 1765). The median HbA(1c) level was 8.2% (interquartile range, 7.6%-9.1%). Significant predictors of HbA1c level in a multiple regression model were duration (b = 0.05; 95% CI, 0.02-0.07) and insulin dose/kg (b = 0.46; 95% CI, 0.27-0.66). At least one episode of severe hypoglycaemia in the previous three months was reported in 6.7%, and the rate of severe hypoglycaemia was 36/100 patient-years. Significant predictors of hypoglycaemia in a Poisson regression model were younger age (P = 0.03), male sex (P = 0.04), longer diabetes duration (P = 0.02), and > 3 daily insulin injections (P = 0.02), but not HbA(1c) level. Children with diabetes had higher BMI standard deviation scores compared with population standards, and those in the highest quartile of BMI standard deviation score were younger, had shorter diabetes duration and had higher HbA(1c) level. CONCLUSIONS: Many children and adolescents with type 1 diabetes have suboptimal glycaemic control, placing them at high risk of developing microvascular complications. Those with longer diabetes duration are at increased risk of suboptimal glycaemic control and severe hypoglycaemia and should be targeted for interventional strategies.

Adolescent↗
PubMed2002

Radical pleurectomy/decortication and intraoperative radiotherapy followed by conformal radiation with or without chemotherapy for malignant pleural mesothelioma.

OBJECTIVES: We performed a retrospective review of the efficacy and morbidity of radical pleurectomy/decortication and intraoperative radiotherapy followed by external beam radiation therapy with or without chemotherapy for diffuse malignant pleural mesothelioma. METHODS: A total of 32 patients with diffuse malignant pleural mesothelioma were initially evaluated between January 1995 and September 2000. Three patients were excluded from analysis because of unresectable disease. Two patients died postoperatively, and one patient had recurrent disease previously treated at an outside institution. Of the remaining 26 patients included in the analysis, 24 received intraoperative radiotherapy. External beam radiation therapy was generally started 1 to 2 months after resection and delivered by means of 3-dimensional conformal radiation therapy or with inverse treatment planning intensity-modulated radiation therapy. When given, chemotherapy consisted of 2 to 3 cycles of cyclophosphamide, doxorubicin (Adriamycin), and cisplatin initiated 1 to 2 months after completion of radiation. RESULTS: At the time of data analysis, 5 of 26 patients were alive. The median follow-up was 9.7 months (range, 2-67.6 months). The median overall survival and progression-free interval from the time of the operation were 18.1 and 12.2 months, respectively. The Kaplan-Meier estimates of overall survival and freedom from progression at 1 year were 64% and 50%, respectively. The site of failure was mostly locoregional. However, there were 4 abdominal failures and 1 contralateral lung failure. CONCLUSIONS: Radical pleurectomy/decortication with aggressive radiotherapy with or without chemotherapy might offer an alternative treatment option to those who cannot tolerate extrapleural pneumonectomy.

Aged↗
PubMed2002

Lead poisoning in new immigrant children from the mainland of China.

OBJECTIVE: To define the prevalence, severity and risk factors for lead poisoning in new immigrant children from the mainland of China to Hong Kong, China. METHODS: New immigrant children from the mainland of China under 18 years of age were invited to join the study. Their growth parameters and venous blood lead levels (BLL) were measured within 7 days of arrival. Those with elevated BLL i.e. > 10 micrograms/dl (0.48 mumol/L) were assessed for signs, symptoms and risk factors of lead poisoning. Education on the prevention of lead poisoning and follow up BLL measurements were offered until their BLL normalized. RESULTS: Four hundred and fifty-seven children were recruited. Among them, 18.1% and 2.6% had BLL > 0.48 and 0.71 mumol/L, respectively. None had BLL > 0.96 mumol/L. Possible risk factors included contaminated drinking water (19%), herb ingestion (17.5%), pica, playing in dumping grounds, residing near paint factories or highways, habitual inhalation of car exhaust and cooking with petroleum. Symptoms and signs included abdominal pain, headache, short stature, and learning difficulties but did not correlate with BLL. None required treatment except for counseling on the avoidance of risk factors. About 94.7% showed a reduction in BLL 2-3 months after arrival and before counseling. All had normalized BLL by 9 months except 1 who had an X-ray feature of lead line. CONCLUSIONS: Lead poisoning is common in new immigrant children from the mainland of China. Environmental factors were most important while behavioral factors like regular herb ingestion might have contributed to the persistence of high BLL in the minority.

Adolescent↗
PubMedDate not supplied

High plantar pressure and callus in diabetic adolescents. Incidence and treatment.

This study examined the incidence of high peak plantar pressure and plantar callus in 211 adolescents with diabetes mellitus and 57 nondiabetic controls. The percentage of subjects with these anomalies was the same in both groups. Although diabetic subjects were no more likely than nondiabetic controls to have high peak plantar pressure and callus, these anomalies place individuals with diabetes at greater risk of future foot problems. The effects of orthoses, cushioning, and both in combination were monitored in 17 diabetic subjects with high peak plantar pressure and in 17 diabetic subjects with plantar callus; reductions of up to 63% were achieved. Twelve-month follow-up of diabetic subjects fitted with orthoses showed a significant reduction in peak plantar pressure even when the orthoses were removed. The diabetic subjects who had not received any interventions during the same 12-month period showed no significant change in peak plantar pressure.

Adolescent↗