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Biomedical subjects

C W Fong

Publications and source records attributed to C W Fong.

13 recordsLinked to original sources
PubMed2006

Changes in the levels of major cardiovascular risk factors in the multi-ethnic population in Singapore after 12 years of a national non-communicable disease intervention programme.

INTRODUCTION: The National Healthy Lifestyle Programme, a population-wide non-communicable disease intervention programme, was started in 1992. A National Health Survey is carried out every six years to evaluate the impact of this programme on the cardiovascular risk factor profile of the resident population of Singapore. METHODS: The 2004 National Health Survey (NHS 04) was a population-based survey carried out over a period of four months from September to December 2004. A combination of disproportionate stratified sampling and systematic sampling was used to select a representative sample (n=7,078) for the survey. The reference population comprised 2.4 million multi-racial Singaporeans aged 18-69 years. Anthropometric and blood pressure measurements were carried out on all subjects and blood samples were taken for biochemical analysis. The results were compared with those of a similar survey conducted in 1998. RESULTS: A total of 4,084 Singapore residents took part in the survey, giving a response rate of 57.7 percent. The age-standardised prevalence of hypertension (greater than or equal to 140/90 mmHg) in Singapore residents aged 30-69 years decreased from 28.0 percent in 1998 to 24.0 percent (p-value is less than 0.001) in 2004. The prevalence of high total cholesterol (greater than or equal to 6.2 mmol/L) among those aged 18-69 years fell from 26.0 percent in 1998 to 18.1 percent (p-value is less than 0.001) in 2004. The prevalence of diabetes mellitus in residents aged 18-69 years in 2004 was 7.8 percent, compared to the 1998 level of 9.5 percent (p-value is less than 0.01). The level of obesity (body mass index is greater than or equal to 30 kg/sqm) increased slightly from 6.2 percent in 1998 to 6.8 percent (p-value equals 0.1627). The prevalence of daily smoking decreased from 15.0 percent in 1998 to 12.5 percent in 2004 (p-value is less than 0.001), while that of regular exercise increased from 17.0 percent to 25.0 percent (p-value is less than 0.001). Ethnic differences in the prevalence of diabetes mellitus, hypertension, hypercholesterolaemia, and exercise were observed. CONCLUSION: The NHS 04 results suggest that the National Healthy Lifestyle Programme significantly decreased daily smoking, high blood cholesterol and hypertension, and increased regular exercise over 1998 levels. The results also suggest that the programme stabilised the prevalence of obesity and diabetes mellitus.

Adolescent↗
PubMed2003

Group IIA secretory phospholipase A2 stimulates exocytosis and neurotransmitter release in pheochromocytoma-12 cells and cultured rat hippocampal neurons.

Recent evidence shows that secretory phospholipase A2 (sPLA2) may play a role in membrane fusion and fission, and may thus affect neurotransmission. The present study therefore aimed to elucidate the effects of sPLA2 on vesicle exocytosis. External application of group IIA sPLA2 (purified crotoxin subunit B or purified human synovial sPLA2) caused an immediate increase in exocytosis and neurotransmitter release in pheochromocytoma-12 (PC12) cells, detected by carbon fiber electrodes placed near the cells, or by changes in membrane capacitance of the cells. EGTA and a specific inhibitor of sPLA2 activity, 12-epi-scalaradial, abolished the increase in neurotransmitter release, indicating that the effect of sPLA2 was dependent on calcium and sPLA2 enzymatic activity. A similar increase in neurotransmitter release was also observed in hippocampal neurons after external application of sPLA2, as detected by changes in membrane capacitance of the neurons. In contrast to external application, internal application of sPLA2 to PC12 cells and neurons produced blockade of neurotransmitter release. Our recent studies showed high levels of sPLA2 activity in the normal rat hippocampus, medulla oblongata and cerebral neocortex. The sPLA2 activity in the hippocampus was significantly increased, after kainate-induced neuronal injury. The observed effects of sPLA2 on neurotransmitter release in this study may therefore have a physiological, as well as a pathological role.

Animals↗
PubMed2002

Seroprevalence of IgG antibodies against Chlamydia pneumoniae in Chinese, Malays and Asian Indians in Singapore.

BACKGROUND: Chlamydia pneumoniae, a bacterium that causes respiratory infections, is probably under-diagnosed. There is also interest in its possible role in the aetiology of coronary heart disease. This is the first population-based seroprevalence survey of C. pneumoniae infection in Singapore. METHODS: A random sample of 1,068 people aged 18-69 years was selected from the participants of the Singapore National Health Survey conducted in 1998. Sera and data on certain clinical measurements and conditions had been collected. IgG antibodies for C. pneumoniae were detected using an indirect microimmunofluorescence test and positivity graded. Seropositivity was defined as IgG titre >/=1:16. RESULTS: There were no statistically significant differences in the prevalence rates of seropositivity to C. pneumoniae for age group 18-69 years among the three ethnic groups, i.e. Chinese (males 76.7%, females 68.3%), Malays (males 75.4%, females 59.1%), and Asian Indians (males 74.6%, females 59.4%). The seropositivity rate for people aged 18-69 years in Singapore was 75.0% for males and 65.5% for females (difference of 9.5%, P < 0.001). In both genders combined, seropositivity increased from 46.5% in the age group 18-29 to reach a plateau of 78.9% in the age group 40-49, which remained stable to 60-69 years. There was no association of seropositivity with smoking, diabetes mellitus, hypertension or body mass index after adjustment for age and gender. CONCLUSION: The high prevalence rates in our study population and the higher rate in males compared to females are consistent with studies from other parts of the world. No significant difference in prevalence rates was observed among Chinese, Malays and Indians. The pattern of rising and levelling off of seropositivity with age suggests that C. pneumoniae infection occurs early in life, and in older ages the high level of seropositivity is probably maintained by re-infections or chronic infections. Chlamydia pneumoniae infection was not found to be associated with the cardiovascular risk factors examined.

Adolescent↗
PubMed2001

Multiple phosphorylation sites in RGS16 differentially modulate its GAP activity.

Regulators of G-protein signaling (RGS) are GTPase-activating proteins (GAP) for activated Galpha subunits. We found that mouse RGS16, when expressed in HEK293T cells, is phosphorylated constitutively at serine 194 based on in vivo orthophosphate labeling experiments, while serine 53 is phosphorylated in a ligand-dependent manner upon stimulation by epinephrine in cells expressing the alpha2A adrenergic receptor. Phosphorylation on both sites impairs its GAP activity and subsequent attenuation on heterotrimeric G-protein-stimulated extracellular signal-regulated protein kinase activity. This is the first report of RGS functional downregulation by phosphorylation via a G-protein-coupled receptor.

Cell Line↗
PubMed2001

Hepatitis B Seroprevalence Study 1999.

Hepatitis B is a disease of public health importance in Singapore. A study was conducted in 1999 to estimate the overall and gender-, age- and ethnic-specific prevalence of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and antibody to hepatitis B surface antigen in the Singapore population. A cross-sectional sample of the Singapore population constituting 4,698 Singapore residents aged 18-69 years was surveyed. This was the first time a large-scale study has been conducted to assess the hepatitis B seroprevalence rates in the Singapore population. The overall prevalence of the HBsAg in the general population was estimated to be about 4%. About 13% of the HBsAg carriers were also HBeAg positive. Only about 40% of the population had immunity to hepatitis B virus either through immunisation or from previous exposure to the virus. There was still a large proportion (60%) of the population who had no immunity, especially the younger age group of 18-29 years where only 28% had immunity. There is a need to strengthen the hepatitis B immunisation programme to reach out to those who have no immunity, especially the young adults.

Adolescent↗
PubMed2000

Specific induction of RGS16 (regulator of G-protein signalling 16) mRNA by protein kinase C in CEM leukaemia cells is mediated via tumour necrosis factor alpha in a calcium-sensitive manner.

The RGS (regulator of G-protein signalling) proteins are GTPase-activating proteins for activated Galpha subunits. We investigated the effects of protein kinase C (PKC) on RGS proteins in various T cell lines by treating them with PMA. mRNA levels of both RGS16 and tumour necrosis factor alpha (TNFalpha) were found to be up-regulated in CEM leukaemia cells in a PKC-dependent manner. Mezerein, a non-phorbol-ester activator of PKC, also elevated RGS16 and TNFalpha mRNA levels, while the specific PKC inhibitor Go6983 abrogated their expression. In view of the slower kinetics of PMA-induced RGS16 expression and the tight correlation between TNFalpha and RGS16 mRNA induction among the cell lines studied, we suggest that activation of PKC up-regulates RGS16 via TNFalpha. Indeed, addition of recombinant TNFalpha to CEM cells rapidly stimulated RGS16 mRNA expression independently of PKC. Furthermore, mobilization of calcium by A23187 and thapsigargin blocked the TNFalpha-mediated induction of RGS16, which was reversed by EGTA and by the immunosuppressants FK506 and cyclosporin A, suggesting that the calcineurin/NF-AT (nuclear factor of activated T cells) pathway may repress the up-regulation process. Our results demonstrate for the first time that activation of PKC induces RGS16 expression via TNFalpha in a calcium-sensitive manner, thereby implicating RGS16 in the regulation of T cell responses to inflammation.

Androstadienes↗
PubMed1999

Analysis of agonist function at fusion proteins between the IP prostanoid receptor and cognate, unnatural and chimaeric G-proteins.

Direct measures of G-protein activation based on guanine nucleotide exchange and hydrolysis are frequently impossible to monitor for receptors which interact predominantly with G(s)alpha. An isolated FLAG (Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys)-epitope-tagged human IP prostanoid receptor and fusion proteins generated between this form of the receptor and the alpha subunits of its cognate G-protein G(s), G(i1), a G-protein which it fails to activate in co-expression studies, and a chimaeric G(i1)-G(s)6 (a form of G(i1) in which the C-terminal six amino acids were replaced with the equivalent sequence of G(s)) were stably expressed in HEK293 cells. These were detected by [(3)H]ligand-binding studies and by immunoblotting with both an anti-FLAG antibody and with appropriate antisera to the G-proteins. Each construct displayed similar affinity to bind the agonist iloprost. Iloprost stimulated adenylate cyclase activity in clones expressing both IP prostanoid receptor and the IP prostanoid receptor-G(s)alpha fusion protein, and both constructs were shown to interact with and activate endogenously expressed G(s)alpha. Addition of iloprost to membranes of cells expressing the isolated receptor resulted in a small stimulation of high-affinity GTPase activity. Iloprost produced no stimulation of GTPase activity which could be attributed to the IP prostanoid receptor-G(i1)alpha fusion. However, the fusion proteins containing either G(s)alpha or G(i1)-G(s)6alpha produced substantially greater stimulation of GTPase activity than the isolated IP prostanoid receptor. Treatment of cells expressing the IP prostanoid receptor-G(i1)-G(s)6alpha fusion protein with a combination of cholera and pertussis toxins allowed direct measurement of agonist activation of the receptor-linked G-protein. Normalization of such results for levels of expression of the IP prostanoid receptor constructs demonstrated a 5-fold higher stimulation of GTPase activity when using the G(s)alpha-containing fusion protein and a 9-fold improvement when using the fusion protein containing G(i1)-G(s)6alpha to detect G-protein activation compared with expression of the isolated receptor.

Adenylate Cyclase Toxin↗
PubMed1998

Selective activation of a chimeric Gi1/Gs G protein alpha subunit by the human IP prostanoid receptor: analysis using agonist stimulation of high affinity GTPase activity and [35S]guanosine-5'-O-(3-thio)triphosphate binding.

A FLAG-tagged form of the human IP prostanoid receptor was expressed stably in HEK 293 cells. This bound [3H]iloprost with high affinity and stimulated cAMP production when exposed to agonist. Iloprost produced weak stimulation of GTPase activity and [35S]guanosine-5'-O-(3-thio)triphosphate binding in membranes of these cells. Pretreatment of cells with pertussis toxin did not modify iloprost-mediated stimulation, but this was blocked by cholera toxin. The effects of iloprost were not increased by coexpression of either Gsalpha or Gi1alpha. In contrast, coexpression of a chimeric G protein alpha subunit in which the carboxyl-terminal six amino acids of Gi1alpha were altered to those of Gsalpha resulted in robust stimulation by iloprost. Because the chimeric G protein alpha subunit (Gi1/Gs6alpha) is not a substrate for either pertussis or cholera toxin, pretreatment of cells coexpressing the IP prostanoid receptor and Gi1/Gs6alpha with a mixture of these toxins resulted in resolution of the signal derived from activation of the chimeric G protein. Agonist-stimulated [35S]guanosine-5'-O-(3-thio)triphosphate binding and GTPase activity assays are the most commonly used strategies to examine interactions between G protein-coupled receptors and G proteins. These usually are not appropriate for receptors such as the IP prostanoid receptor that interact with G proteins with low rates of guanine nucleotide exchange and hydrolysis. Chimeric G proteins such as Gi1/Gs6alpha that allow appropriate receptor contacts to be converted to the higher nucleotide turnover rates typical of the Gi family G proteins can overcome this and offer a novel means to examine agonist function at such receptors.

Cell Line↗
PubMed1995

Characterization of protein complexes formed on the repressor elements of the human tumor necrosis factor alpha gene.

Human tumor necrosis factor alpha (TNF-alpha) is an important cytokine responsible for pleiotropic effects in vivo. The expression of TNF-alpha is under both positive and negative regulation. Previously we showed that a 108 bp region (-280 to -172) in the TNF-alpha promoter represses TNF-alpha transcription in U937 cells. We also demonstrated that a smaller region of the promoter spanning base pairs -254 and -230 is sufficient for repressor function. This 25 bp TNF-alpha repressor site (TRS) contains a 10 bp sequence homologous to the binding site of activator protein AP-2, yet it does not bind the AP-2 protein. In this study, we demonstrate that this 10 bp core sequence is an essential element for the repressor function of the TRS. Using gel retardation analysis with the 108 bp repressor element and the TRS as probes, multiple specific DNA binding complexes have been identified from U937 nuclear extracts. The complexes B, C, and D on the 108 bp probe and the three major complexes on the 25 bp TRS probe are also present in Jurkat and Mono Mac 6 cells, and their abundance in these cell lines seems to correlate with their postulated repressor function. We have demonstrated that the major TRS binding proteins, with estimated MWs of 30-60 kD, copurify on a heparin agarose column and on a DNA affinity column conjugated with the 10 bp core sequence.

Base Sequence↗
PubMed1978

An evaluation of ultraviolet radiation personnel hazards from selected 400-watt high intensity discharge lamps.

A study of selected mercury and multi-vapor lamps, commonly used for working environment illumination, was underta ken to evaluate the scope of the ultraviolet personnel hazards one may expect under various operating conditions of the lamps. Spectral irradiance measurements were made for operating conditions with and without reflector-type luminaires, glass covers on luminaries and outer glass bulbs on the lamps.

Environmental Exposure↗