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Biomedical subjects

H M Chan

Publications and source records attributed to H M Chan.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of tumor growth and metastasis in vitro and in vivo by targeting macrophage migration inhibitory factor in human neuroblastoma.

Macrophage migration inhibitory factor (MIF) has been defined as a novel oncogene. Our previous results have shown that MIF may contribute to the progression of neuroblastoma by (a) inducing N-Myc expression and (b) upregulating the expression of angiogenic factors. The aim of this study was to test whether tumor growth could be inhibited by reduction of endogenous MIF expression in neuroblastoma and clarify the molecular mechanisms underlying MIF reduction on the control of neuroblastoma growth. We established human neuroblastoma cell lines stably expressing antisense MIF (AS-MIF) cDNA. These stable transfectants were characterized by cell proliferation, gene expression profile, tumorigenicity and metastasis in vitro and in vivo. Decreased MIF expression was observed after transfection with AS-MIF in neuroblastoma cells and downregulation of MIF expression significantly correlated with decreased expression of N-Myc, Ras, c-Met and TrkB at protein level. Affymetrix microarray analysis revealed that expression of IL-8 and c-met was inhibited and neuroblastoma-favorable genes such as EPHB6 and BLU were upregulated in MIF reduced cells. Neuroblastoma cell growth exhibited a nearly 80% reduction in AS-MIF transfectants in vitro. Furthermore, mice in which tumors formed after subcutaneous injection of AS-MIF transfectants showed a 90% reduction in tumor growth compared to control. Metastasis in mice was also suppressed dramatically. Our data demonstrate that targeting MIF expression is a promising therapeutic strategy in human neuroblastoma therapy, and also identifies the MIF target genes for further study.

Animals↗
PubMed2006

Selection criteria for recipients of scarce donor livers: a public opinion survey in Hong Kong.

OBJECTIVE: To explore the public preference in determining the selection criteria for recipients of scarce donor livers. DESIGN: Structured interview survey. SETTING: Hong Kong community. PARTICIPANTS: Participants from Hong Kong households, randomly drawn from 18 districts in Hong Kong by the Census and Statistics Department. MAIN OUTCOME MEASURES: Age of patients, causes of liver failure, capacity for survival and benefit, time spent on the waiting list, and transplantation status. RESULTS: A total of 281 participants were recruited with the response rate of 26.2%. In all sections of the questionnaire, there was a strong preference for the young over the old, non-drinkers over drinkers, those more likely to survive, those who had waited longest on the list, and primary candidates over re-transplant candidates. Approximately 91% of participants agreed or strongly agreed that priority should be given to patients most likely to survive and benefit from a liver transplant, and 39% of participants also ranked 'survival and benefit' as the most important criterion in determining allocation of donor livers. Nonetheless when participants were asked to allocate a finite number (100) of donor livers to two groups of individuals with different characteristics in a set of eight hypothetical scenarios, they preferred giving priority to patients who had waited longer on the waiting list. CONCLUSION: Although comparatively the general public surveyed had dominant preferences to maximise benefit and survival, they were unlikely to rely on one criterion for allocation. Overall cost-effectiveness of the intervention was not the sole deciding factor.

Adolescent↗
PubMed2005

Effects of nontoxic shot regulations on lead accumulation in ducks and American woodcock in Canada.

Prior to the first nontoxic shot zones being established in Canada, a nationwide survey of lead (Pb) concentrations in wing bones of hatch year (HY) dabbling and diving ducks determined the incidence of elevated Pb exposure in waterfowl in different parts of the country (Scheuhammer and Dickson 1996). The main objectives of the present study were (1) to compare these previously collected data with the incidence of elevated Pb accumulation in the same species several years after the establishment of a national regulation in 1997 prohibiting the use of Pb shot for waterfowl hunting; and (2) to survey waterfowl hunters to determine reported levels of compliance with the nontoxic shot regulation. Average bone-Pb concentrations in dabbling ducks (mallards [Anas platyrhyncos] and American black ducks [Anas rubripes] combined) decreased significantly between 1989+1990 and 2000 (11 microg/g vs. 4.8 microg/g, respectively [p < 0.01]). Ring-necked ducks (Aythya collaris) showed a similar decrease in mean bone-Pb concentrations, from 28 microg/g to 10 microg/g (p < 0.01). These declines in bone-Pb concentration were consistent with the results of a large anonymous hunter survey, which indicated a high level of reported compliance (>80%) with the nontoxic shot regulation among waterfowl hunters residing in Ontario and British Columbia. Conversely, American woodcock (Scolopax minor), an important upland game species not affected by the nontoxic shot regulation, showed no decrease in mean bone-Pb concentration since the national regulation came into effect (19 microg/g in 1995 vs. 21 microg/g in 2000). A majority (70%) of waterfowl hunters in British Columbia and Ontario who also hunt upland game birds report continued (legal) use of Pb shot for upland game bird hunting.

Animals↗
PubMed2005

Growth, nutritional composition, and hematology of Arctic charr (Salvelinus alpinus) exposed to toxaphene and tapeworm (Diphyllobothrium dendriticum) larvae.

Toxaphene, an organochlorine pesticide, is the major contaminant of Arctic charr (Salvelinus alpinus) in the Canadian Arctic. The objective of this study was to investigate the combined effects of toxaphene exposure and infection by the larval stage of the cestode Diphyllobothrium dendriticum on fish growth, nutritional composition, and hematology. Hatchery-reared Arctic charr were subjected to one of four treatments: (1) oral administration of corn oil (control); (2) single oral dose of 10 microg/g wet wt toxaphene dissolved in corn oil; (3) exposure to 15 larval D. dendriticum; and (4) exposure to toxaphene and D. dendriticum in combination. The experiment was run for 104 days. Mean final toxaphene concentrations in charr muscle were 0.121, 0.336, 0.131 and 0.458 microg/g wet wt in each treatment group, respectively. Exposure to toxaphene and D. dendriticum decreased fish growth and condition as well muscle lipid and protein content. However, toxaphene did not increase the susceptibility of Arctic charr to parasite infection. Overall, 25 of 40 fish (62.5%) exposed to larval D. dendriticum became infected. Parasitized charr had decreased hematocrits and increased lymphocyte:erythrocyte ratios. Although total blood cell counts were decreased in all treatments compared with controls, differential leucocyte counts were unaffected. Our results suggest that toxaphene does not moderate Arctic charr resistance to D. dendriticum and there is no contaminant-parasite interaction at environmental levels.

Animals↗
PubMed2003

Assessment of white blood cell phagocytosis as an immunological indicator of methylmercury exposure in birds.

White blood cell (WBC) phagocytosis was investigated as a potential immunological indicator of methylmercury (MeHg) exposure in birds. The assay was first assessed using chicken WBCs dosed with MeHg in vitro either in whole blood or as isolated cells and later using blood of wild common loons exposed in vivo to a range of dietary MeHg and having a range of blood-Hg concentrations. Whole blood and isolated WBCs from captive chickens were exposed to a range of MeHg concentrations for 3 h. After MeHg exposure, cells were incubated with fluorescent latex microbeads (diameter = 1.75 microm), fixed, and analyzed for size, complexity, and fluorescent intensity by flow cytometry. MeHg significantly depressed phagocytic activity when added to isolated WBCs at concentrations > 0.01 microg/ml, but not when added to whole blood up to 50 microg/ml. Similarly, no significant relationship between the concentration of Hg in whole blood and phagocytic capacity of WBCs in free-living loons was observed. Our results suggest that the phagocytosis assay, although rapid and convenient for use in field studies with wildlife species, is not a responsive immunological indicator of MeHg exposure at environmentally realistic concentrations of blood-Hg in wild loons. Assays that measure other immunologic endpoints (e.g., bacterial killing assay, PHA skin test, and mitogen-induced lymphocyte proliferation) should be assessed with respect to their ability to detect MeHg immunotoxicity in wild birds.

Animals↗
PubMed2001

Role of LXCXE motif-dependent interactions in the activity of the retinoblastoma protein.

Cell cycle control by pRb requires the integrity of the pocket domain, which is a region necessary for interactions with a variety of proteins, including E2F and LXCXE-motif containing proteins. Through knowledge of the crystal structure of pRb we have prepared a panel of pRb mutant derivatives in which a cluster of lysine residues that demark the LXCXE peptide binding domain were systematically mutated. One of the mutant derivatives, Rb6A, exhibits significantly reduced LXCXE-dependent interactions with HPV E7, cyclinD1 and HDAC2, but retained LXCXE-independent binding to E2F. Consistent with these results, Rb6A could down-regulate E2F-1-dependent activation of different E2F responsive promoters, but was compromised in Rb-dependent repression. Most importantly, Rb6A retained wild-type growth arrest activity, and colony forming activity similar to wild-type pRb. It is compatible with these results that directly targeting HDAC2 to E2F responsive promoters as an E2F/HDAC hybrid protein failed to effect cell cycle arrest. These results suggest that LXCXE-dependent interactions are not essential for pRb to exert growth arrest.

Amino Acid Motifs↗
PubMed2001

Organotins in zebra mussels (Dreissena polymorpha) and sediments of the Quebec City Harbour area of the St. Lawrence River.

Toxic antifouling agents such as tributyltin (TBT) and triphenyltin (TPT) have been released in aquatic ecosystems through the use of antifouling paint applied to ship hulls, pleasure crafts and fish nets and these compounds can bioaccumulate in aquatic organisms. The purpose of this study was 1) to assess the extent of the distribution of organotins from a contaminated marina to the St. Lawrence River system by measuring organotin concentrations in zebra mussels (Dreissena polymorpha) and in sediments collected from 9 sites along the St. Lawrence River near Quebec City in July 1998, and 2) to examine the histopathological condition of zebra mussel tissues from these sites. TBT concentrations in zebra mussels were between 37 and 1078 ng Sn g(-1) wet weight, with the highest value found in the Bassin Louise marina. Elevated concentrations were also found in two other marinas. The concentrations decreased sharply to background levels just outside the marinas. All butyltins were detected in all sediments analysed, with highest values found in the Bassin Louise marina. Phenyltins were detected in three of the nine sites in low concentrations (<55 ng Sn g(-1)) in zebra mussels. There was a significant correlation between TBT in sediments and mussels. Gonadal development of zebra mussels varied largely between sites, and was negatively associated to TBT levels in mussel tissue. This study shows that TBT contamination remains a problem in localised freshwater sectors of the St. Lawrence River.

Animals↗
PubMed2001

Acetylation control of the retinoblastoma tumour-suppressor protein.

The retinoblastoma tumour-suppressor protein (pRb) and p300/CBP co-activator proteins are important for control of proliferation and in tumour cells these are sequestered by viral oncoproteins such as E1A. pRb is involved in negatively regulating growth, and p300/CBP proteins have histone acetyltransferase (HAT) activity, which influences gene expression. Although it is known that phosphorylation by G1 cyclin-dependent kinases (CDKs) regulates pRb activity, the nature and role of other post-translational modifications is not understood. Here we identify acetylation as a new type of modification and level of control in pRb function. Adenovirus E1A, which binds p300/CBP through an amino-terminal transformation-sensitive domain, stimulates the acetylation of pRb by recruiting p300 and pRb into a multimeric-protein complex. Furthermore, pRb acetylation is under cell-cycle control, and acetylation hinders the phosphorylation of pRb by cyclin-dependent kinases. pRb binds more strongly when acetylated to the MDM2 oncoprotein, which indicates that acetylation may regulate protein-protein interactions in the pRb pathway. The acetylation of pRb defines a new level of cell-cycle control mediated by HAT. Furthermore, our results establish a relationship between p300, pRb and acetylation in which E1A acts to recruit and target a cellular HAT activity to pRb.

Acetylation↗
PubMed2001

The glycaemic index values of Vietnamese foods.

OBJECTIVE: To determine and compare the glycaemic index (GI) values of a range of Vietnamese foods in two racial groups. DESIGN AND SUBJECTS: Twelve healthy subjects (six Asian and six Caucasian) consumed 50 g carbohydrate portions of a reference food (glucose sugar) and nine Vietnamese foods (three rices, three noodle products and three sweet foods) in random order after an overnight fast. The reference food was tested on two separate occasions, and the Vietnamese foods were each tested once. Capillary blood samples were taken at time 0 (fasting), 15, 30, 45, 60, 90 and 120 min from the start of each meal. Samples were analysed for plasma glucose and the incremental areas under the plasma glucose curves (AUC) were used to calculate the GI values of the test foods, using glucose as the reference food (ie GI value of glucose=100). The mean GI value of each food was calculated for the entire group of subjects (n=12) and for both racial groups (n=6). RESULTS: The three rices had surprisingly high GI values (86-109), whereas the noodle products had relatively low GI values (39-61). The sugar-rich foods produced intermediate GI values (54-79). The GI values for the nine foods calculated separately for the two racial groups were not significantly different from each other (P=0.26). CONCLUSIONS: The GI values derived from Caucasian subjects are likely to be applicable to Asian populations. Varieties of imported rice from Thailand were found to have high GI values. Alternative low-GI staples, such as rice noodles, may be preferable for Asian/Vietnamese people with diabetes. SPONSORSHIP: This study was funded by the University of Sydney.

Animals↗
PubMed2001

Control of gene expression and the cell cycle.

The pRb tumour suppressor protein is an essential component of the cell-cycle clock, integrating both positive and negative signals for cellular growth and proliferation with the transcription machinery. pRb exerts its tumour suppression function by both antagonizing and synergizing with downstream effectors, such as E2F. pRb has two modes of action, it can inactivate E2F transcription activity or it can assemble an active repression complex with E2F. Apart from E2F, pRb interacts with various factors to promote cellular differentiation. The differentiation properties of pRb are likely to contribute partly to its tumour suppressor function. It is also clear that pRb is a master regulator for transcription. It can both activate and repress transcription in a context-dependent manner. pRb interacts directly with histone acetyltransferase, histone deacetylases and SWI/SNF proteins, all of which are classes of proteins involved in chromatin remodelling. Last, but not least, pRb regulates transcription driven by all three polymerases, thereby integrating the cell-cycle clock with the biosynthetic capacity of the cell in controlling cellular proliferation and growth.

Animals↗
PubMed2001

Cadmium in caribou (Rangifer tarandus) kidneys: speciation, effects of preparation and toxicokinetics.

Caribou kidney is a major source of cadmium (Cd) in the traditional diets of many aboriginal communities in the Arctic. In order to characterize the risk of Cd exposure, we studied the speciation of Cd in caribou kidneys and how, it can be affected by food preparation. Cd in caribou kidneys was bound to metallothionein (MT) (40%) high molecular weight proteins (50-500 kDa) (30%) and existed as free ions (10%). There was no change in Cd concentrations after the samples were baked at 350 degrees C for 30 min but the MT level was significantly decreased. Food preparation also denatured the high molecular weight proteins, resulting in a significant increase of free Cd. The toxicokinetics of Cd in caribou kidney was studied using a rodent model. Four groups (n = 6) of adult Sprague-Dawley rats were fed with rat chow with the addition of one of the following: 10% veal kidney with 0 microg/g Cd, 10% veal kidney spiked with CdCl2 to make up to 66 microg Cd; 10% caribou kidney containing 20 microg/g Cd and 10% caribou kidney containing 66 microg/g Cd. After 14 days, Cd accumulation increased with dose but less than 1% of the dosed Cd accumulated in the liver and kidney of rats. The percentage of Cd accumulated in the liver was higher in the group fed with caribou kidney than that dosed with spiked veal kidney. Our results suggest that caribou kidney is a major source of Cd exposure among the Arctic populations but moderate consumption may be considered unavoidable.

Absorption↗
PubMed2001

Phylogenetic analysis of enterovirus 71 strains isolated during linked epidemics in Malaysia, Singapore, and Western Australia.

Enterovirus 71 (EV71) is a frequent cause of hand, foot, and mouth disease (HFMD) epidemics associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case fatality rates. In this study, we show that four genetic lineages of EV71 have been prevalent in the Asia-Pacific region since 1997, including two previously undescribed genogroups (B3 and B4). Furthermore, we show that viruses belonging to genogroups B3 and B4 have circulated endemically in Southeast Asia during this period and have been the primary cause of several large HFMD or encephalitis epidemics in Malaysia, Singapore, and Western Australia.

Amino Acid Sequence↗
PubMed2001

p300/CBP proteins: HATs for transcriptional bridges and scaffolds.

p300/CBP transcriptional co-activator proteins play a central role in co-ordinating and integrating multiple signal-dependent events with the transcription apparatus, allowing the appropriate level of gene activity to occur in response to diverse physiological cues that influence, for example, proliferation, differentiation and apoptosis. p300/CBP activity can be under aberrant control in human disease, particularly in cancer, which may inactivate a p300/CBP tumour-suppressor-like activity. The transcription regulating-properties of p300 and CBP appear to be exerted through multiple mechanisms. They act as protein bridges, thereby connecting different sequence-specific transcription factors to the transcription apparatus. Providing a protein scaffold upon which to build a multicomponent transcriptional regulatory complex is likely to be an important feature of p300/CBP control. Another key property is the presence of histone acetyltransferase (HAT) activity, which endows p300/CBP with the capacity to influence chromatin activity by modulating nucleosomal histones. Other proteins, including the p53 tumour suppressor, are targets for acetylation by p300/CBP. With the current intense level of research activity, p300/CBP will continue to be in the limelight and, we can be confident, yield new and important information on fundamental processes involved in transcriptional control.

Acetyltransferases↗
PubMed2001

Traditional food systems research with Canadian Indigenous Peoples.

Traditional food systems research with Canadian Indigenous Peoples has revealed many aspects of benefits and risks of the use of this food. Traditions based in hunting, fishing and gathering contain a great variety of species of wildlife plants and animals that provide rich cultural and nutritional benefits. Dietary change for Indigenous Peoples in Canada has resulted in the use of traditional food to provide usually less than 30% of total dietary energy; however this portion of the total diet contributes significantly more of essential nutrients. It also results in exposure to organochlorine and heavy metal contaminants that exceed the tolerable intake levels for some areas. A successful research and education intervention program with one British Columbia community demonstrated that increasing traditional food use can improve health status for vitamin A, iron and folic acid. It is concluded that traditional food systems are rich with potential for research and public health education intervention programs for Indigenous Peoples.

Canada↗
PubMed2000

A pharmacokinetic model for predicting absorption, elimination, and tissue burden of toxaphene in rats.

A two-compartment pharmacokinetic model was formulated to predict absorption, elimination, and tissue burden of toxaphene in rats. The model was constructed based on the database of Crowder and Dindal (Bull. Environ. Contam. Toxicol. 12, 320-327, 1974) and included six tissue compartments: blood, brain, liver, muscle, fat, and carcass. The pharmacokinetically based dosimetry indicated that absorption of toxaphene was fast in fat, whole body, carcass, and blood, relatively slow in liver and muscle, and slow in brain. In contrast, the elimination rate was rapid in whole body, muscle, and blood, moderate in carcass and brain, and slow in liver and fat. Tissue burden was highest in fat, whole body, and blood, intermediate in liver, and lowest in brain. The model performance was evaluated by the data set of Pollock and Hillstrand (J. Environ. Sci. Health B 17, 635-648, 1982) on toxaphene absorption and elimination in pregnant rats. Validity of the model was confirmed by the close agreement between the predicted and observed tissue burdens of toxaphene in target tissues. Disposition of toxaphene via feces was a dominant excretory pathway while urinary excretion was a minor elimination route in male rats. However, for pregnant rats, excretion of toxaphene both in urine and feces were of similar magnitude. These characteristics of elimination are valuable for understanding the metabolism of toxaphene in pregnant rats. The model serves as a starting point for a quantitative, mechanism-based understanding of the processes that influence the pharmacokinetics of toxaphene in mammalian systems.

Algorithms↗
PubMed2000

Total toxaphene and specific congeners in fish from the Yukon, Canada.

Toxaphene is one of the major persistent organic pollutants with global environmental impacts. We have measured total toxaphene and specific congeners concentrations in 19 fish samples collected from the Yukon, Canada using gas chromatography coupled to ion trap MS/MS. The total toxaphene concentrations ranged from 42 to 242 ng/g (mean = 107+/-61 ng/g). The sum of the three specific congeners (Parlar 26, 50 and 62) was within 10-55 ng/g. The ratio of the sum of the three congeners to the total toxaphene varied between 8% and 25% in the fish samples but the ratio may be species specific. Our results suggest that consumption of these Yukon fish should have minimal risk of toxaphene exposure.

Animals↗