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H Chan

Publications and source records attributed to H Chan.

At least 19 recordsLinked to original sources
PubMed2006

Development of an interactive learning tool for teaching rheumatology--a simulated clinical case studies program.

OBJECTIVES: To promote independent self-study involving problem solving and decision analysis in the undergraduate medical curriculum, we have developed a series of interactive web-based clinical case studies. METHODS: An initial needs assessment was performed to determine students' attitudes to e-learning. From these results we designed a series of 30 interactive case studies for delivery from a web-server. RESULTS: A survey of 59 undergraduate students believed that online teaching resources were a useful supplement to existing teaching and they could see a positive use for e-learning. The interactive case studies program was well received by a broad range of respondents (n = 84) of different abilities and backgrounds who felt that the program was realistic and clearly presented in an intuitive manner. CONCLUSIONS: The recent increases in numbers of medical undergraduates, the trend towards student-centred learning and the emphasis on patient-related teaching means a great pressure on teachers and resources in medical schools. The case studies program we have developed was effective and well received by both biomedical and medical students. This approach may provide a way to increase the exposure of students to clinical cases involving interactive diagnostic and treatment procedures, that mimic real-world scenarios, but with fewer resource implications.

Computer Simulation↗
PubMed2006

Aging and mfERG topography.

AIM: To study the effect of aging retina on the multifocal electroretinogram (mfERG). METHODS: A total of 18 young subjects (age 18-24 years) and 36 elderly subjects (aged 60-85 years) with intraocular lenses (IOLs) were recruited for this study. No subjects had significant eye diseases or media opacities. mfERG was measured in standard conditions using the VERIS system (version 4.1). There were three groups of 18 subjects: (1) 18-25 years, (2) 60-70 years, and (3) 75-85 years. mfERG responses were grouped into central, paracentral, and peripheral regions for analysis. The N1 amplitude, P1 amplitude, N1 latency, and P1 latency of the first-order responses were analysed. RESULTS: Age had no effect on P1 latency, N1 amplitude, and P1 amplitude; however, N1 latencies from central to peripheral regions were significantly longer for group 3 than for group 1. CONCLUSIONS: This study suggests that measured age-related decreases in mfERG responses are due to optical factors (decrease in retinal light levels, scatter) before the age of 70 years, but neural factors significantly affect mfERG topography after the age of 70 years.

Adult↗
PubMed2005

Heat shock protein 70 and tumor necrosis factor alpha in Taiwanese patients with dementia.

This study was to determine whether polymorphisms of heat shock protein 70-1 (HSP70-1) and tumor necrosis factor alpha (TNF-alpha) are associated with the risk of Alzheimer's disease (AD) and vascular dementia (VaD). Using the criteria of the NINCDS-ADRDA and NINDS-AIREN, 125 AD patients, 57 VaD patients and 109 ethnically matched nondemented controls were enrolled. The HSP70-1 -110 A/C and TNF-alpha -1031 T/C, -863 C/A and -857 C/T polymorphisms were analyzed by means of genotype or haplotype association methods. None of the four genotypes examined showed a statistically significant difference in genotype distribution between the AD cases and controls. However, the HSP70-1 -110 CC genotype occurred more frequently among AD cases (p=0.0821; odds ratio: 2.08; 95% confidence interval, CI: 0.92-4.98). The overall genotype distribution among the VaD cases tended to be different at the HSP70-1 -110 and TNF-alpha -1031 sites (p=0.0604 and 0.0316, respectively). The HSP70-1 -110 CC genotype was more frequent (p=0.0459), and the association of the -110 CC genotype with VaD was evident (p=0.0207; odds ratio: 3.22; 95% CI: 1.20-8.87). The more frequent TNF-alpha -1031 TC genotype (p=0.0614) was also evidently associated with VaD (p=0.0209; odds ratio: 2.32; 95% CI: 1.14-4.78). Multivariate analysis demonstrated the synergistic effect of the HSP70-1 -110 CC and TNF-alpha -1031 TC/CC genotypes on VaD (p=0.0091; odds ratio: 10.09; 95% CI: 2.01-75.97). Haplotype analysis among TNF-alpha -1031, -863, -857 sites revealed that -1031C-857C may act as a risk haplotype among VaD cases (p=0.0132, odds ratio: 2.26; 95% CI: 1.19-4.33). Our results suggest a potential protective role for HSP70 in both VaD and AD, whereas TNF-alpha may act as a risk factor only for VaD, and not for AD.

Aged↗
PubMed2005

A retrospective review of visual outcome and complications in the treatment of retinoblastoma.

The aim of this study was to look at the visual outcome and treatment complications of children diagnosed with Retinoblastoma during the years 1985-2003 inclusive. A retrospective review of all patients records was performed. Patient characteristics, treatment methods and complications were recorded. Twenty eight children presented to Temple street Hospital between 1985-2003. Six of these infants had bilateral tumours. The mean age at presentation was 23.7 months. Sixty-nine percent presented with Leucocoria, of these 33% also had a squint. The mean duration of symptoms was only known in 58% and this figure was approximately 19.8 months. Enucleation was performed in 24 eyes of 24 patients. Three patients required adjuvant chemotherapy post enucleation. Two eyes was treated with external beam radiation and one eye with plaque radiotherapy. One eye (second eye) was treated with systemic chemotherapy and radiation. Five eyes of three patients were treated with systemic chemotherapy followed by adjuvant Argon laser, cryotherapy and diode laser to each eye.The complications of each treatment group was recorded. The visual outcome in the salvaged eyes was favourable. There were no deaths recorded. Though chemotherapy with adjuvant local treatments provide adequate treatment for early tumours, enucleation still plays a major role in the treatment of Retinoblastoma. The total eye salvage rate in this study was 29% with an enucleation rate of 90% in unilateral cases and 33% in bilateral cases. Sixty-six percent of bilateral eyes affected were salvaged. Seventy-one percent of tumours were diagnosed after a parent noticed a gross abnormality of the eye. This highlights the possible need for screening for retinoblastoma in the infant population.

Chemotherapy, Adjuvant↗
PubMed2004

Pityriasis rosea--evidence for and against an infectious aetiology.

Pityriasis rosea, first named as such in 1860, probably holds the longest record for an exanthem suspected to be associated with an infection but for which an exact cause has not been found. The distinctly programmed clinical course, the lack of recurrence for most patients, and the presence of temporal case clustering provide the strongest evidence to support an infectious aetiology. Further support comes from seasonal variation and the association with respiratory tract infections, the unfavourable social and economic background of cases, and a history in some cases of contact with patients with pityriasis rosea. The apparent therapeutic efficacy of several treatment modalities does not provide strong evidence for or against an infectious aetiology. The roles of human herpesvirus 7 and to a lesser extent human herpesvirus 6 remain controversial. There exists reasonable evidence that pityriasis rosea is not associated with cytomegalovirus, Epstein-Barr virus, parvovirus B19, picornavirus, influenza and parainfluenza viruses, Legionella spp., Mycoplasma spp. and Chlamydia spp. infections. Evidence is also unsubstantiated as yet for alternative aetiological hypotheses such as autoimmunity, atopy, and genetic predisposition.

Bacterial Infections↗
PubMed2004

Allogeneic bone marrow transplantation vs chemotherapy for children with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Allogeneic bone marrow transplant (BMT) with an MRD in complete remission (CR)1 is the preferred treatment for children with Philadelphia-positive (Ph(+)) ALL. The role of MUD BMT in CR1 is still controversial. We compared the outcomes of two treatment strategies: BMT using an MRD or MUD vs chemotherapy in children with Ph(+) ALL in CR1. In total, 21 children were treated from 1985 to 2001. In all, 10 received chemotherapy and 11 received allogeneic BMT: four MRD, seven MUD. In the MRD group, one relapsed 12 months after BMT and died; the remaining three are long-term event-free survivors (median follow-up, 6.1 years). In the MUD group four died; the remaining three are long-term event-free survivors (median follow-up, 7.2 years). The 4-year event-free survival (EFS) for the BMT group was 53+/-15%. In the chemotherapy group, seven relapsed after a median period of 12.5 months and three remain in continuous CR (median follow-up, 2.4 years). Four chemotherapy patients received CR2 transplants; all died. The 4-year EFS for the chemotherapy and MUD groups was 33+/-17 and 35.7+/-20%, respectively. This difference was not statistically significant. We continue to support treating children with Ph(+) ALL with MRD BMT in CR1. The effectiveness of MUD BMT vs chemotherapy merits further study.

Adolescent↗
PubMed2004

Effects of different degrees of cataract on the multifocal electroretinogram.

AIM: To study the effect of different degrees of nuclear cataract on the multifocal electroretinogram (mfERG). METHODS: mfERGs were recorded from 30 elderly subjects with very mild, mild, or moderate nuclear cataracts using a VERIS System (version 4.1). The subjects were divided into three groups (10 in each group) according to their degree of nuclear cataracts as classified according to the Lens Opacities Classification System III (LOCS III). No subjects had any significant eye disease or degenerative changes except for cataracts. The mfERG responses were grouped into six concentric rings for analysis. Both the N1 and P1 amplitudes and the latencies of N1 and P1 of first-order responses were used for analysis. RESULTS: Amplitudes of N1 and P1 from the central retina (14 degrees) were significantly reduced in patients with mild or moderate cataract when compared with subjects with very mild cataract. However, there was no significant reduction of N1 and P1 amplitudes in the para-central retina (14-40 degrees). There was no difference in the latencies of N1 and P1 in these three groups of subjects. CONCLUSIONS: The mfERG responses from the central retina (central 14 degrees) were affected by the severity of cataract, but responses from the paracentral retina (14-40 degrees) were not affected. This suggests that in interpreting the mfERG in subjects with mild or moderate cataract subjects some care should be taken as reduced amplitudes (N1 and P1) will be expected from the central retina.

Aged↗
PubMed2004

Variable left ventricular activation pattern in patients with heart failure and left bundle branch block.

OBJECTIVE: To determine the left ventricular (LV) activation pattern in patients with chronic heart failure and left bundle branch block (LBBB) on ECG. DESIGN: Prospective study. SETTING: Tertiary cardiology referral centre in Hong Kong. PATIENTS: Seven patients with LV ejection fraction < 35% and typical LBBB on ECG with QRS duration > or = 130 ms were recruited. Five of them had non-ischaemic dilated cardiomyopathy. METHODS: Non-contact mapping was used to investigate the LV global activation sequences. Tissue Doppler imaging was performed with the LV mapping and correlated with the activation sequences. RESULTS: Three patients had preserved left bundle activation despite LBBB on ECG. Conduction block was detected in four patients during LV activation and the other three had homogeneous depolarisation propagation within the left ventricle. The latest segment of activation was located in either the lateral or the posterior region. Tissue Doppler imaging correlated well with non-contact mapping to locate the conduction block and the latest segment of activation. CONCLUSIONS: LV endocardial activation sequences in patients with chronic heart failure and LBBB are variable. This may have implications for patient selection for treatment with cardiac resynchronisation.

Aged↗
PubMed2004

Evaluation of the protective effectiveness of gloves from occupational exposure to 2-methoxyethanol using the biomarkers of 2-methoxyacetic acid levels in the urine and plasma.

AIMS: To evaluate the protective effectiveness of gloves from occupational exposure to 2-methoxyethanol (2-ME); and to examine the association of 2-methoxyacetic acid (MAA) in urine and plasma collected simultaneously from low 2-ME exposure and high 2-ME exposure workers in a semiconductor copper laminate circuit board manufacturing plant. METHODS: Eight hour time weighted breathing zone monitoring was performed to verify the 2-ME exposure classification between workers in regular and special operations. Urine and plasma samples were simultaneously collected from 74 exposed and 80 non-exposed workers. MAA concentrations in the urine (UMAA) and plasma (PMAA) were measured using previously published methods. Three types of gloves worn by workers (cotton, rubber, and no gloves) were recorded by direct observations in the workplace and validated by person-to-person interview. Protective effectiveness indices (PEI) were used to evaluate the glove effectiveness. RESULTS: There was no detectable 2-ME/MAA in the air, or in urine and plasma samples in non-exposed workers. The average UMAA and PMAA in special operations were 72.63 mg/g Cr. and 29.72 mg/l, significantly higher than values in regular operations (5.44 mg/g Cr. and 2.58 mg/l, respectively). PMAA showed satisfactory correlation to UMAA in all participants from both regular and special operations. The rubber gloves provided significant reduction in 2-ME uptake, whereas cotton gloves provided little protection with fluctuating effectiveness, based on PEI estimates. CONCLUSIONS: PMAA, similar to UMAA, could serve as a specific biomarker for 2-ME exposure. Wearing impermeable rubber gloves during high risk tasks can reduce major 2-ME exposure. Other improvements, including engineering control, should be provided to diminish worker exposure to 2-ME in occupational environments.

Acetates↗
PubMed2002

Biochemical and immunocytochemical characterization of calsenilin in mouse brain.

Mutations in the presenilin 1 and 2 genes cause the majority of early onset familial forms of Alzheimer's disease. Here we describe the biochemical and immunohistochemical characterization of calsenilin, a novel calcium binding protein that we have previously shown to interact with presenilins 1 and 2, in mouse brain. The co-immunoprecipitation of endogenous calsenilin and presenilin 1 demonstrates that these proteins are physiologic binding partners. Although calsenilin has been predicted to be a soluble protein, we have found that the majority of it is tightly associated with the cytoplasmic face of intracellular membranes and that it can only be dissociated using harsh treatments such as urea. In addition, we have demonstrated that calsenilin is a developmentally regulated protein that is mainly present in the brain, where it localizes to both the hippocampus and cerebellum. Calsenilin staining co-localized with the somatodendritic marker microtubule-associated protein-2 primarily in the granular cell layer of the cerebellum, indicating that calsenilin expression is primarily neuronal. In primary cultured neurons, calsenilin immunoreactivity was observed in cell bodies as well as in some neuronal processes. Co-localization experiments using specific axonal and dendritic markers indicate that these processes were mainly axonal in nature, although a smaller subset of dendrites also appears to contain calsenilin. In summary, we have established that calsenilin and presenilin 1 can interact at physiologic levels, and that calsenilin is a developmentally regulated protein that is expressed primarily in the cerebellum and hippocampus. Although calsenilin is a soluble protein, it is tightly associated with the membrane. Finally, the expression pattern of calsenilin, which is similar to that of the presenilin(s), suggests that the common locations of these two proteins provide an opportunity for physical interaction in vivo.

Aging↗
PubMed2001

Subcellular localization of presenilin 2 endoproteolytic C-terminal fragments.

Mutations in the genes that encode the presenilin 1 and 2 (PS1 and PS2) proteins cause the majority of familial Alzheimer's disease (FAD). Differential cleavage of the presenilins results in a generation of at least two C-terminal fragments (CTFs). An increase in the smaller of these two CTFs is one of the few changes in presenilin processing associated with FAD mutations in both PS1 and PS2. Interestingly, the phosphorylation of PS2 modulates the production of the smaller, caspase-derived PS2 CTF, which indicates that the generation of this fragment is a regulated, physiologic event. To date, there is no data concerning the subcellular distribution of the caspase-derived PS2 CTF. Because this fragment is normally present at levels that are difficult to detect, we have used cell lines in which the production of wild-type or N141I mutant PS2 is controlled by a tetracycline-regulated promoter in order to assess the subcellular localization of the caspase CTF in relation to the larger, constitutive PS2 CTF and to PS2 holoprotein. We have found that when levels of PS2 are low, the constitutive CTF colocalizes with markers consistent with localization in the early Golgi-ER-Golgi intermediate compartment (ERGIC) while the caspase CTF colocalizes with markers for the endoplasmic reticulum (ER). Following induction of wild-type or mutant PS2, when the levels of PS2 are high, the primary localization of the constitutive CTF appears to shift from the early Golgi-ERGIC in addition to the ER. Interestingly, while the induction of wild-type PS2 resulted in the localization of the caspase CTF primarily in the ER, the induction of mutant PS2 resulted in the localization of the caspase CTF to both the ER and the early Golgi-ERGIC. In summary, these data suggest that the two presenilin 2 CTFs have different patterns of subcellular localization and that the N141I PS2 mutation alters the localization pattern of the PS2 caspase fragment.

Alzheimer Disease↗
PubMed2001

A link between the synthesis of nucleoporins and the biogenesis of the nuclear envelope.

The nuclear pore complex (NPC) is a multicomponent structure containing a subset of proteins that bind nuclear transport factors or karyopherins and mediate their movement across the nuclear envelope. By altering the expression of a single nucleoporin gene, NUP53, we showed that the overproduction of Nup53p altered nuclear transport and had a profound effect on the structure of the nuclear membrane. Strikingly, conventional and immunoelectron microscopy analysis revealed that excess Nup53p entered the nucleus and associated with the nuclear membrane. Here, Nup53p induced the formation of intranuclear, tubular membranes that later formed flattened, double membrane lamellae structurally similar to the nuclear envelope. Like the nuclear envelope, the intranuclear double membrane lamellae enclosed a defined cisterna that was interrupted by pores but, unlike the nuclear envelope pores, they lacked NPCs. Consistent with this observation, we detected only two NPC proteins, the pore membrane proteins Pom152p and Ndc1p, in association with these membrane structures. Thus, these pores likely represent an intermediate in NPC assembly. We also demonstrated that the targeting of excess Nup53p to the NPC and its specific association with intranuclear membranes were dependent on the karyopherin Kap121p and the nucleoporin Nup170p. At the nuclear envelope, the abilities of Nup53p to associate with the membrane and drive membrane proliferation were dependent on a COOH-terminal segment containing a potential amphipathic alpha-helix. The implications of these results with regards to the biogenesis of the nuclear envelope are discussed.

Active Transport, Cell Nucleus↗
PubMed2001

A linkage analysis of sex determination in Bombus terrestris (L.) (Hymenoptera: Apidae).

We constructed a linkage map of Bombus terrestris (Hymenoptera, Apidae) phase unknown. The map contains 79 markers (six microsatellite and 73 RAPD markers) in 21 linkage groups and spans over 953.1 cM. The minimal recombinational size of the B. terrestris genome was estimated to be 1073 cM. Using flow cytometry, the physical size of the haploid genome of B. terrestris was calculated to be 274 Mb. This is the second linkage map for a social insect species. Bombus terrestris has on average five times less recombinational events per kb than the honey bee Apis mellifera. Male haploidy, chromosome size, and eusociality can now be excluded as reasons for the high recombination frequency of Apis mellifera. Finally, the sex determination locus of B. terrestris was placed on the map using bulked segregant analysis.

Animals↗
PubMed2001

Effects of injection duration on site-pain intensity and bruising associated with subcutaneous heparin.

AIM: The research evaluated two subcutaneous heparin injection techniques to determine the effects of different injection duration (10- and 30-seconds) on site-pain intensity and bruising. BACKGROUND: The research was instigated because nurses and patients in the hospital under investigation reported a high incidence of site-pain and bruising associated with subcutaneous heparin therapy. This research was conducted over a period of 7 months between September 1998 and April 1999. The Ethic Committees of the University and the hospital approved the research. METHODS: The research used a within-subjects, quasiexperiment, which would yield more convincing causal inferences, owing to the assumption that pain perception and physiological factors affecting coagulation varied less in the same subject than in two comparable subjects. The research involved 34 stroke patients receiving low-molecular weight heparin. For each subject, one of the two injection techniques was used as the first injection and 12 hours later the other injection technique as the second injection. Subjects rated the level of perceived site-pain intensity using the vertical visual analogue scale (VAS). Injection-site bruising were measured at 48 and 60 hours after each injection. Digital planimetry was used to measure the surface-area of bruise tracings. The final data set for analysis consisted of 68 VAS pain scores and 136 bruise sizes. As normality of the data could not met after transformations, Wilcoxon Signed-Rank tests were used to determine the effects caused by injection duration on site-pain and bruise size. The level of significance was determined at P < 0.05. RESULTS: Results indicated that the 30-second duration injection technique resulted in significantly less intense site-pain and fewer and smaller bruises. CONCLUSIONS: It was concluded that administering a subcutaneous heparin injection over longer duration reduces injection site-pain and bruising. However, the convenience, relatively small sample may limit the generalisability of the research findings.

Adult↗
PubMed2000

Granulocyte-macrophage colony-stimulating factor inhibits HIV-1 replication in monocyte-derived macrophages.

BACKGROUND: Previous studies of the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on HIV-1 replication in macrophages have had inconsistent results, variously reporting no effect, augmentation or inhibition of viral replication. OBJECTIVE: To investigate the regulation of HIV-1 in monocyte-derived macrophages (MDM) by GM-CSF in vitro. METHODS: The role of GM-CSF on HIV-1 replication was assessed as supernatant and intracellular p24 antigen concentrations and by HIV-1 DNA and mRNA production under different culture conditions. Expression of CD4 and CCR5 receptors was examined. The effect of GM-CSF with an E21R mutation, which binds only to the alpha-chain of GM-CSF receptor, was used as an additional control. RESULTS: GM-CSF consistently suppressed HIV-1 replication in human MDM in vitro, as assessed by supernatant and intracellular p24 antigen concentrations and HIV-1 gag mRNA expression. The inhibitory effect of GM-CSF on HIV-1 replication was observed regardless of HIV-1 strain, source of GM-CSF, stage of MDM maturation or timing of GM-CSF exposure in relation to HIV-1 infection. The effect was dose dependent and reversed by addition of a neutralizing monoclonal antibody (4D4). Flow cytometric analysis of surface expression of CD4 and CCR5 indicates that GM-CSF does not affect HIV-1 entry into MDM. Analysis of intracellular HIV-1 DNA and mRNA suggests that HIV-1 replication is inhibited at or before transcription. E21R GM-CSF had no effect on HIV-1 replication in MDM. CONCLUSIONS: GM-CSF regulates HIV-1 replication in MDM, inhibiting HIV-1 replication through binding to the beta-chain of the GM-CSF receptor.

Cells, Cultured↗
PubMed2000

Fusion of small peroxisomal vesicles in vitro reconstructs an early step in the in vivo multistep peroxisome assembly pathway of Yarrowia lipolytica.

We have identified and purified six subforms of peroxisomes, designated P1 to P6, from the yeast, Yarrowia lipolytica. An analysis of trafficking of peroxisomal proteins in vivo suggests the existence of a multistep peroxisome assembly pathway in Y. lipolytica. This pathway operates by conversion of peroxisomal subforms in the direction P1, P2-->P3-->P4-->P5-->P6 and involves the import of various peroxisomal proteins into distinct vesicular intermediates. We have also reconstituted in vitro the fusion of the earliest intermediates in the pathway, small peroxisomal vesicles P1 and P2. Their fusion leads to the formation of a larger and more dense peroxisomal vesicle, P3. Fusion of P1 and P2 in vitro requires cytosol and ATP hydrolysis and is inhibited by antibodies to two membrane-associated ATPases of the AAA family, Pex1p and Pex6p. We provide evidence that the fusion in vitro of P1 and P2 peroxisomes reconstructs an actual early step in the peroxisome assembly pathway operating in vivo in Y. lipolytica.

ATPases Associated with Diverse Cellular Activitie↗