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Biomedical subjects

B Chan

Publications and source records attributed to B Chan.

At least 19 recordsLinked to original sources
PubMed2006

Validation of a geographic information system model for mapping the risk of fasciolosis in cattle and buffaloes in Cambodia.

Maps showing gradations of risk of fasciolosis due to Fasciola gigantica in Cambodia were produced using geographic information systems (GIS) technology in conjunction with determinants of fasciolosis. A comparison between levels of risk predicted by the maps and field measurements of prevalence in 11 provinces (n=1406) showed general agreement, which suggested the epidemiological determinants and weightings used to produce the maps were appropriate. However, due to logistical constraints, prevalence was measured at the provincial level and animals were not randomly sampled (and thus were unlikely to be representative of variability within provinces). To address this, additional field work was carried out to measure prevalence in more detail--faecal samples were collected from a randomly selected set of animals in four districts across a representative province for areas predicted to be at high risk (n=311), moderate risk (n=268) and no risk (n=262). As with the original field survey, the results show general agreement between prevalence and risk predicted by the maps, with the best fit found for areas predicted to be at high risk.

Animals↗
PubMed2005

Oral health sensations associated with illicit drug abuse.

OBJECTIVES: To investigate oral health sensations (short term oral health effects) associated with illicit drug abuse. In addition, to identify variations in oral health sensations produced by different illicit drugs. SUBJECT: Young adults in a drug rehabilitation programme in Hong Kong, China. METHOD: Self-completed questionnaire about their previous pattern of drug abuse and oral health sensations experienced (recalled). RESULTS: All (119) subjects were poly-drug abusers (abused one or more illicit drugs in the past). Amphetamine-based drugs such as methamphetamine ('speed') and methylenedioxymethamphetine ('ecstasy') were commonly abused. A wide range of oral health sensations were reported on recall of their abuse of illicit drugs; most frequently dry mouth (95%, 113). Types of illicit drugs abused were associated with oral health sensations reported (P < 0.001). 'Ecstasy' abusers more frequently reported chewing (P < 0.001), grinding (P < 0.001), and TMJ tenderness (P < 0.001) compared to non-'ecstasy' abusers. CONCLUSION: Illicit drug abuse produces many oral health sensations. Types of drugs abused were associated with oral sensations produced. and behavioural effects that may manifest as depression, anxiety, memory loss and various neuropsychotic disorders.(8),(9) In some cases drug abuse can result in death by various means: malignant hyperthermia, internal bleeding, fatal overdosing and through allergic reactions.(10),(11) Likewise, there have been reports on the long term clinical effects of illicit drug abused on oral health.

Adolescent↗
PubMed2004

Hydroxyapatite-coated, cementless total knee replacement in patients aged 75 years and over.

We have carried out a prospective study comparing the results at five years in patients older than 75 years of age undergoing hydroxyapatite-coated, cementless total knee replacement (TKR) with those who were younger. The Knee Society clinical rating scores were recorded before and after operation. Of 559 patients undergoing TKR, 135 were in the elderly age group. The knee scores at five years or more showed comparable results, with patients under 75 years of age reaching a score of 183 and those aged 75 years or over reaching 174. These differences were predominantly due to the functional component of the score. We conclude that elderly patients do just as well as the younger group using this prosthesis.

Adult↗
PubMed2003

Adoptive cellular immunotherapy for non-small cell lung cancer: a pilot study.

BACKGROUND: Priming with autologous tumor vaccine followed by ex vivo expansion of activated T cells is a feasible experimental strategy. This paper describes the application of this cellular therapy to treat patients with late-stage non-small-cell lung cancer (NSCLC). METHODS: Twenty-one patients with Stages III and IV NSCLC were treated. Tumor samples were obtained surgically (five patients) or by using aco-axial biopsy needle (16 patients). Each course of vaccination consisted of irradiated tumor cells, mixed with GM-CSF and injected intradermally on Day 1, followed by GM-CSF only on Days 2- 5. The course was repeated 10-14 days later. Lymphocytes were collected 10-14 day after the second course and ex vivo expanded using IL-2 and anti-CD3 Ab. The expansion products were then re-infused into the patients. RESULTS: Twelve out of 16 biopsies resulted in optimal cell numbers for vaccine preparation. Nineteen out of 21 patients achieved a delayed type hypersensitivity (DTH response after two courses of vaccination. In 18/21 patients, the ex vivo expansion products contained > 1.6 x 10(10) cells. Subset analysis showed 77.0-97.2% T cells with a CD4:CD8 ratio of 0.65-4.0; natural killer cells were 2.0-18.6%. There were no significant toxicities. The median survival of all 21 patients was 18.6 months, with a 1-year survival of 51.6%. CONCLUSION: Autologous tumor cell-vaccination may be combined with ex vivo expansion of lymphocytes as adoptive cellular immunotherapy for advanced NSCLC. Overall survival in this cohort of poor prognosis patients compared favorably with results reported in the literature.

Carcinoma, Non-Small-Cell Lung↗
PubMed2002

The effect of chronic insulin delivery via the intraperitoneal versus the subcutaneous route on hepatic triglyceride secretion rate in streptozotocin diabetic rats.

Chronic intraperitoneal or subcutaneous insulin administration increases triglyceride secretion rate (TGSR) in normal rats. We wished to determine the effect of this treatment on TGSR and the hepatic lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in diabetic rats. Streptozotocin-diabetic rats, untreated (D), diabetic rats treated with insulin (3 U/day for 21 days) intraperitoneally (IP) or subcutaneously (SC) and non-diabetic rats (N) were studied. TGSR was determined using Triton WR-1339. Fasting glucose and triglyceride levels, high in D, were normalized by insulin treatment regardless of route. Peripheral insulin levels were lowest in D and highest in SC, portal insulin levels were lowest in D and highest in IP. Non-esterified fatty acid levels were not elevated in D, presumably due to adipose tissue depletion. TGSR was reduced in D (P<0.05) and was normalized following insulin administration, regardless of route. ACC activity was normal, but FAS was decreased in D (P<0.05). ACC and FAS were normal in both IP and SC. Thus, in streptozotocin-diabetic rats, chronic intraperitoneal or subcutaneous insulin treatment increases TGSR and FAS activity from their low levels in insulin-deficient rats to levels equal to but not higher than those in normal rats.

Acetyl-CoA Carboxylase↗
PubMed2002

Public opinion on smoke-free policies in restaurants and predicted effect on patronage in Hong Kong.

BACKGROUND: The Hong Kong government has proposed legislation for smoke-free policies in all restaurants and bars. This is opposed by certain sections of the catering industry. OBJECTIVE: To assess public opinion on smoke-free restaurants and to estimate changes in patronage. DESIGN: A population based, cross sectional random digit dialling telephone survey conducted from November 1999 to January 2000. SETTING AND PARTICIPANTS: 1077 randomly selected subjects age 15 years or over (response fraction of 81.6%). RESULTS: 68.9% (95% confidence interval (CI) 66.2% to 71.7%) supported a totally smoke-free policy in restaurants. Experiences of discomfort or symptoms from second hand smoke in restaurants were common. The majority (77.2%, 95% CI 74.7% to 79.7%) anticipated no change in their frequency of use of restaurants after a smoke-free policy. Increased use was predicted by 19.7% (95% CI 17.3% to 22.1%) of respondents, whereas 3.2% (95% CI 2.2% to 4.4%) stated that they would dine out less often. In multivariate analyses, non-smokers (adjusted odds ratio (OR) 4.9), people who ate three times or less per week in restaurants as compared to those who ate >10 times per week (OR 2.1), those who had previous experience of discomfort from exposure to passive smoking in restaurants (OR 2.8), or who had avoided restaurants in the past because of smoking (OR 1.9), were more likely to support a totally smoke-free policy in restaurants. Smoke-free policies do not appear to have an adverse effect on restaurants, and may increase business by a considerable margin. CONCLUSION: This comprehensive survey-the first in Asia-shows strong community support for smoke-free dining and predicts an overall increase in the patronage of restaurants after the introduction of legislation for totally smoke-free restaurants.

Adolescent↗
PubMed2001

Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency.

BLyS (also called BAFF, TALL-1, THANK, and zTNF4), a TNF superfamily member, binds two receptors, TACI and BCMA, and regulates humoral immune responses [1-7]. These two receptors also bind APRIL [7-10], another TNF superfamily member. The results from TACI(-/-) and BCMA(-/-) mice suggest the existence of additional receptor(s) for BLyS. The TACI knockout gives the paradoxical result of B cells being hyperresponsive, suggesting an inhibitory role for this receptor [11, 12], while BCMA null mice have no discernable phenotype [13]. Here we report the identification of a third BLyS receptor (BR3; BLyS receptor 3). This receptor is unique in that, in contrast to TACI and BCMA, BR3 only binds BLyS. Treatment of antigen-challenged mice with BR3-Fc inhibited antibody production, indicating an essential role for BLyS, but not APRIL, in this response. A critical role for BR3 in B cell ontogeny is underscored by our data showing that the BR3 gene had been inactivated by a discrete, approximately 4.7 kb gene insertion event that disrupted the 3' end of the BR3 gene in A/WySnJ mice, which lack peripheral B cells.

Amino Acid Sequence↗
PubMed2001

Consistency analysis of similarity between multiple alignments: prediction of protein function and fold structure from analysis of local sequence motifs.

A new method to analyze the similarity between multiply aligned protein motifs (blocks) was developed. It identifies sets of consistently aligned blocks. These are found to be protein regions of similar function and structure that appear in different contexts. For example, the Rossmann fold ligand-binding region is found similar to TIM barrel and methylase regions, various protein families are predicted to have a TIM-barrel fold and the structural relation between the ClpP protease and crotonase folds is identified from their sequence. Besides identifying local structure features, sequence similarity across short sequence-regions (less than 20 amino acid regions) also predicts structure similarity of whole domains (folds) a few hundred amino acid residues long. Most of these relations could not be identified by other advanced sequence-to-sequence or sequence-to-multiple alignments comparisons. We describe the method (termed CYRCA), present examples of our findings, and discuss their implications.

Adenosine Triphosphatases↗
PubMed2001

A study of demographic changes under sustained below-replacement fertility in Hong Kong SAR.

The total fertility in Hong Kong SAR fell continuously below replacement in the past two decades and reached a level of 0.98 in 1998. The rate in 1981 was close to replacement at 1.93. In this paper the theoretical outcomes of long-lasting below-replacement fertility are identified with a view to gaining some analytical insight into the situation, where the population is experiencing such a striking demographic trend. In the absence of migration, Hong Kong SAR will see its population start to decline between 2008 and 2038, if the future course of fertility falls within these 'bounds'. Concurrently, the aging of population will be reaching unprecedented proportions. Should fertility remain at the present below-replacement level, i.e. the worse-case scenario, the proportion of population aged 65 years or older would increase to 44 per cent, and those aged under 15 years would decrease to six per cent, by 2048. As a result, the potential labour supply (those aged 15-64 years) would dwindle to only 50 per cent of the population, suggesting that there would be less than one person potentially working to support one dependent (who is likely to be a person aged 65 years or older). The socio-economic consequences of population aging are discussed. By analysing net immigration in the demographic process in the past, the way in which replacement migration would help alleviate the problem of population decline and population aging is also discussed.

Adolescent↗
PubMed2001

Cell surface glypicans are low-affinity endostatin receptors.

Endostatin, a collagen XVIII fragment, is a potent anti-angiogenic protein. We sought to identify its endothelial cell surface receptor(s). Alkaline phosphatase- tagged endostatin bound endothelial cells revealing two binding affinities. Expression cloning identified glypican, a cell surface proteoglycan as the lower-affinity receptor. Biochemical and genetic studies indicated that glypicans' heparan sulfate glycosaminoglycans were critical for endostatin binding. Furthermore, endostatin selected a specific octasulfated hexasaccharide from a sequence in heparin. We have also demonstrated a role for endostatin in renal tubular cell branching morphogenesis and show that glypicans serve as low-affinity receptors for endostatin in these cells, as in endothelial cells. Finally, antisense experiments suggest the critical importance of glypicans in mediating endostatin activities.

3T3 Cells↗
PubMed2001

TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice.

Interactions of the tumor necrosis factor superfamily members B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) with their receptors-transmembrane activator and CAML interactor (TACI) and B cell maturation molecule (BCMA)-on B cells play an important role in the humoral immune response. Whereas BCMA is restricted to B cells, TACI is also expressed on activated T cells; we show here that TACI-Fc blocks the activation of T cells in vitro and inhibits antigen-specific T cell activation and priming in vivo. In a mouse model for rheumatoid arthritis (RA), an autoimmune disease that involves both B and T cell components, TACI-Fc treatment substantially inhibited inflammation, bone and cartilage destruction and disease development. Thus, BLyS and/or APRIL are important not only for B cell function but for T cell-mediated immune responses. Inhibition of these ligands might have therapeutic benefits for autoimmune diseases, such as RA, that involve both B and T cells.

Animals↗
PubMed2001

Activation and accumulation of B cells in TACI-deficient mice.

The tumor necrosis factor (TNF)-related ligand B lymphocyte stimulator (BLyS) binds two TNF receptor family members, transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI) and B cell maturation molecule (BCMA). Mice that are transgenic for BLyS show B cell accumulation, activation and autoimmune lupus-like nephritis. The existence of at least two distinct BLyS receptors raises the question of the relative contribution of each to B cell functions. We therefore generated mice that were deficient in TACI. TACI-/- mice showed increased B cell accumulation and marked splenomegaly. Isolated TACI-/- B cells hyperproliferated and produced increased amounts of immunoglobulins in vitro. In vivo antigen challenge resulted in enhanced antigen-specific antibody production. Thus, TACI may play an unexpected inhibitory role in B cell activation that helps maintain immunological homeostasis.

Animals↗
PubMed2001

Anti-IgE efficacy in murine asthma models is dependent on the method of allergen sensitization.

BACKGROUND: Murine models used to delineate mechanisms and key mediators of asthma have yielded conflicting results and suggest that the dominant mechanism and mediators required for disease induction differ depending on the model and method of allergen sensitization used. OBJECTIVE: The goal of this study was to determine whether the mode of allergen sensitization influenced the role that IgE had in allergen-induced pulmonary eosinophilic inflammation. METHODS: Mice were exposed to dust mite extract in 2 models of allergic inflammation that differed in the method of sensitization. We compared sensitization by aerosol exposure with and without concomitant human respiratory syncytial virus infection with sensitization by means of systemic (intraperitoneal) exposure with adjuvant. After sensitization, animals were similarly challenged with aerosolized allergen. Animals were treated with anti-IgE mAb to deplete IgE and to determine its role in the induction of allergic inflammation and mucosa pathology in these models. RESULTS: Concomitant respiratory syncytial virus infection significantly enhanced allergen sensitization by aerosol exposure and exacerbated eosinophilic inflammation and airway mucosa pathology. Depletion of IgE in this model significantly reduced lung eosinophilic inflammation and airway mucosa pathology. However, in the model in which animals were sensitized by means of systemic allergen exposure with adjuvant, depletion of IgE had no ameliorative effect on lung inflammation or pathology. CONCLUSION: We demonstrated that the method of antigen sensitization can delineate the role of IgE in allergen-induced lung inflammation. In a murine model that more closely resembles ambient allergen exposure in human subjects, IgE had a critical role in the pathogenesis of allergic asthma and mucosa pathology. The results parallel the results reported with anti-IgE efficacy in allergic asthmatic human subjects.

Allergens↗
PubMed2001

Increased cell proliferation and associated expression of PDGFRbeta causing hypercellularity in patellar tendinosis.

OBJECTIVE: This study assessed cellularity in patellar tendinosis with respect to cell proliferation and the expression of platelet-derived growth factor receptor beta (PDGFRbeta). METHODS: Surgical samples were taken from 11 patients fulfilling criteria of patellar tendinosis and from 12 matched controls. Standard immunohistochemistry methods were used to detect expression of PDGFRbeta and proliferation cell nuclear antigen (PCNA). Results were analysed by computer-assisted microscopy. Tendon cells were isolated from nine tendinosis and eight control tissues for cell culture. RESULTS: Increased cellularity (P<0.001) was observed in tendinosis tissues compared with controls, and also a higher proliferative index (P:<0.001). Increased expression of PDGFRbeta was demonstrated (P<0.001). Cultured tendinosis cells showed a higher proliferation rate than controls (P<0.001). This was maintained when the cells were cultured under various conditions of serum supplementation (P<0.01). Tendinosis cells also showed a higher proliferation rate (P<0.01) in medium containing 10 ng/ml PDGF. CONCLUSION: Hypercellularity in patellar tendinosis is caused by increased cell proliferation and is associated with increased expression of PDGFRbeta.

Adolescent↗
PubMed2001

On-line detection of sleep-wake states and application to produce intermittent hypoxia only in sleep in rats.

Sleep-disordered breathing is associated with adverse clinical consequences such as daytime sleepiness and hypertension. The mechanisms behind these associations have been studied in animal models, especially rats, but intermittent stimuli such as hypoxia have been applied without reference to sleep-wake states. To determine mechanisms underlying the adverse physiological consequences of stimuli associated with sleep-disordered breathing requires criteria for detection of sleep-wake states on-line to trigger stimuli only in sleep. This study aimed to develop such a system for freely behaving rats. Twelve rats with implanted electroencephalogram and neck electromyogram electrodes were studied in the light and dark phases. Electroencephalogram frequencies in the high (20-30 Hz) and low (2-4 Hz) frequency bands distinguished non-rapid eye movement (REM) sleep, whereas neck electromyogram distinguished REM. Using these parameters in a simple algorithm led to detection accuracies of 94.5 +/- 1.0 (SE) % for wakefulness, 96.2 +/- 0.8% for non-REM sleep, and 92.3 +/- 1.6% for REM compared with blinded human judgment. The algorithm was then used to trigger hypoxic stimuli only in sleep. Because frequency and amplitude analysis is readily performed using a variety of commercial systems, incorporation of these parameters into such an algorithm will facilitate studies investigating mechanisms underlying the physiological consequences of sleep-related respiratory stimuli in a fashion that more effectively models clinical disorders.

Algorithms↗
PubMed2001

Myopia in Singapore kindergarten children.

PURPOSE: The purpose of this study was to examine whether close-up work was related to myopia in Singapore kindergarten children. METHODS: One hundred twenty-eight children, ages 3 to 7 years, from a kindergarten in Singapore were examined by cycloplegic autorefraction. The parents also completed a questionnaire on the different types of close-up work activities each child was engaged in, socioeconomic status, and parental history of myopia. RESULTS: Myopic children spent 3.0 hours per day (median) on close-up work activity, while nonmyopic children spent 2.0 hours per day (median) on close-up work activity. The prevalence of myopia in the sample was 8.6%. CONCLUSION: Close-up work activity was not related to myopia in pre-school children.

Child↗
PubMed2000

Evolutionary coadaptation of the motif 2--acceptor stem interaction in the class II prolyl-tRNA synthetase system.

Known crystal structures of class II aminoacyl-tRNA synthetases complexed to their cognate tRNAs reveal that critical acceptor stem contacts are made by the variable loop connecting the beta-strands of motif 2 located within the catalytic core of class II synthetases. To identify potential acceptor stem contacts made by Escherichia coli prolyl-tRNA synthetase (ProRS), an enzyme of unknown structure, we performed cysteine-scanning mutagenesis in the motif 2 loop. We identified an arginine residue (R144) that was essential for tRNA aminoacylation but played no role in amino acid activation. Cross-linking experiments confirmed that the end of the tRNA(Pro) acceptor stem is proximal to this motif 2 loop residue. Previous work had shown that the tRNA(Pro) acceptor stem elements A73 and G72 (both strictly conserved among bacteria) are important recognition elements for E. coli ProRS. We carried out atomic group "mutagenesis" studies at these two positions of E. coli tRNA(Pro) and determined that major groove functional groups at A73 and G72 are critical for recognition by ProRS. Human tRNA(Pro), which lacks these elements, is not aminoacylated by the bacterial enzyme. An analysis of chimeric tRNA(Pro) constructs showed that, in addition to A73 and G72, transplantation of the E. coli tRNA(Pro) D-domain was necessary and sufficient to convert the human tRNA into a substrate for the bacterial synthetase. In contrast to the bacterial system, base-specific acceptor stem recognition does not appear to be used by human ProRS. Alanine-scanning mutagenesis revealed that motif 2 loop residues are not critical for tRNA aminoacylation activity of the human enzyme. Taken together, our results illustrate how synthetases and tRNAs have coadapted to changes in protein-acceptor stem recognition through evolution.

Adaptation, Biological↗