Biomedical subjects

J S Tay

Publications and source records attributed to J S Tay.

At least 19 recordsLinked to original sources

PubMed1995

Inflammatory response in bacterial meningitis: cytokine levels in the cerebrospinal fluid.

Inflammatory response plays an important role in the pathogenesis of cerebral injury in bacterial meningitis. In this study, we evaluated the cytokine levels of interleukin 1-beta (IL1 beta), tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) in the cerebrospinal fluid (CSF), and determined their correlation with acute clinical complications and with changes in CSF biochemistry. Interleukin 6, TNF alpha and IL1 beta were present in 9/9, 3/9 and 4/9 patients, respectively. The CSFs with detectable TNF alpha or IL1 beta had higher levels of IL6 (p < 0.02), protein (NS) and lower glucose levels (p < 0.02), compared with those in which TNF alpha and IL1 beta were absent. Tumour necrosis factor alpha and IL1 beta levels also correlated with the presence of prolonged fever, fits, spasticity and death (logTNF alpha: r = 0.70, p < 0.05; logIL1 beta: r = 0.62, p = 0.08). The cytokine levels reflect the degree of inflammatory response and are positively correlated with the severity of acute clinical complications. Modulation of this inflammatory response in bacterial meningitis may improve its morbidity and mortality.

Acute Disease↗

PubMed1995

Population genetic study among the Orange Asli (Semai Senoi) of Malaysia: Malayan aborigines.

A population genetic study was undertaken to provide gene frequency data on the additional blood genetic markers in the Semai and to estimate the genetic relations between the Semai and their neighboring and linguistically related populations by genetic distance and principal components analyses. Altogether 10 polymorphic and 7 monomorphic blood genetic markers (plasma proteins and red cell enzymes) were studied in a group of 349 Senoi Semai from 11 aboriginal settlements (villages) in the Pahang State of western Malaysia. Both the red cell glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (PGD) loci reveal the presence of polymorphic frequencies of a nondeficient slow allele at the G6PD locus and a fast allele at the PGD locus. The Semai are characterized by high prevalences of ahaptoglobinemia and G6PD deficiency, high frequencies of HP*1, HB*E, RH*R1, ACP*C, GLO1*1, PGM1*2+, and GC*1F and corresponding low frequencies of ABO*A, HbCoSp, HB*B0, TF*D, CHI, and GC*2. Genetic distance analyses by both cluster and principal components models were performed between the Semai and 14 other populations (Malay; Javanese; Khmer; Veddah; Tamils of Malaysia, Sri Lanka, and India; Sinhalese; Oraon; Toda and Irula of India; Chinese; Japanese; Koreans) on the basis of 30 alleles at 7 polymorphic loci. A more detailed analysis using 53 alleles at 13 polymorphic loci with 10 populations was carried out. Both analyses give genetic evidence of a close relationship between the Semai and the Khmer of Cambodia. Furthermore, the Semai are more closely related to the Javanese than to their close neighbors--the Malay, Chinese, and Tamil Indians. There is no evidence for close genetic relationship between the Semai and the Veddah or other Indian tribes. The evidence fits well with the linguistic relationship of the Semai with the Mon-Khmer branch of the Austro-Asiatic language family.

Adolescent↗

PubMed1994

Molecular characterisation of red cell glucose-6-phosphate dehydrogenase deficiency in Singapore Chinese.

Sixty-two G6PD deficient Chinese males have been investigated for the presence of seven mutations of the coding region of the G6PD gene by natural and artificially created amplified restriction sites. The results show that the G to T substitution at nucleotide (nt) 1376 and G to A substitution at nt 1388 represent 24% and 21% of G6PD deficiency, respectively, in the Singapore Chinese; 37% of the sample could not be characterised. The remaining samples were identified as follows: 10% C-->T at nt 563, 5% A-->G at nt 95, and 3% C-->T at nt 1024. The G to A substitution (nt 487) and the substitution A-->G (nt 493) were not present in this sample. None of the subjects with the Mediterranean mutation (563 C-->T) had the silent mutation at 1311 (C-->T). This study confirms the extreme molecular heterogeneity of the G6PD gene in the Chinese.

Base Sequence↗

PubMed1994

Influence of polymorphisms for apolipoprotein B (ins/del, XbaI, EcoRI) and apolipoprotein E on serum lipids and apolipoproteins in a Javanese population.

A total of 231 healthy subjects from a central Javanese population were investigated for the distribution of three apolipoprotein B (apo B) polymorphisms (ins/del, XbaI, and EcoRI), as well as apolipoprotein E (apo E) polymorphism in relation to serum lipid and apolipoprotein concentrations. The frequencies of the rarer alleles (del, 0.09; X+, 0.1; and R-, 0.06) were lower than have been found for some Asian and European populations. Distribution of genotypes was in Hardy-Weinburg equilibrium for all the polymorphisms. A linkage disequilibrium was observed only between the ins/del and XbaI site polymorphisms of apo B (chi 2(4)) = 25.3; P < 0.001) consistent with that observed in some other population studies. No polymorphism of the apo B gene had an association with serum lipid or apolipoprotein concentrations in this population except for XbaI, which appeared to be associated with serum TG (as the log transform: R2 = 8.3; F = 4.8; P < 0.01). The apo E4 allele was found to be associated with significantly higher serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC). Apo E polymorphism explained 5.9% of the sample variance of serum LDLC (F = 5.4; P < 0.01).

Adolescent↗

PubMed1994

Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI levels in Chinese non-smokers.

The influence of the guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein (apo) AI gene (at -75 bp) on serum lipids and apolipoproteins was studied in 287 healthy Chinese of both sexes in Singapore. Women had significantly higher levels of high-density lipoprotein cholesterol (HDLC) and apo AI and lower low-density lipoprotein cholesterol (LDLC). The distribution of genotypes was at Hardy-Weinberg equilibrium. The frequency of the A allele in the Chinese was significantly higher [0.27; 95% confidence interval (CI) 0.24-0.31] than that reported in Caucasians (0.12; 95% CI 0.09-0.14). In men, the A allele was associated with 20% higher apo AI; this association was completely absent in women. Furthermore, in men this association was only observed in those who had never smoked, and was absent in smokers. The G/A substitution explained 9% (P < 0.02) of the sample variance of apo AI in non-smoking men. The modulating influence of smoking could not be examined in women because too few women smoke. Although the impact of this polymorphism is modulated by hormones and smoking, it is of importance in determining levels of apo AI in healthy Chinese individuals. No association of the G/A substitution of the apo AI gene was observed with any other lipid traits.

Adenine↗

PubMed1994

The amplification refractory mutation system (ARMS): a rapid and direct prenatal diagnostic technique for beta-thalassaemia in Singapore.

beta-Thalassaemia major patients have chronic anaemia and since 3-4 per cent of Singaporeans carry the beta-gene, prenatal diagnosis is essential. We evaluated the amplification refractory mutation system (ARMS) technique as a routine test for prenatal diagnosis of beta-major. Six mutations along the beta-gene were studied--41-42 (-TCTT), IVSII #654 (C-T), 17 beta (A-T), -28 TATA (A-G), IVSI #5 (G-C), and IVSI #1 (G-T). Our results indicate that prenatal diagnosis using these mutations can be offered to 90 per cent (35/39) of our Chinese couples and 54.6 per cent (12/22) of our Malay couples at risk. Confirmation of ARMS results was carried out using allele-specific oligonucleotide hybridization. Prenatal diagnosis using ARMS was successfully carried out in nine cases which included a set of triplets and twins. The triplets were diagnosed with the beta-trait carrying the 41-42 mutation. The couple with twins possessed the #654 mutation and one twin was diagnosed with the beta-trait and the other with #654 homozygosity. Genomic sequencing of the undefined mutations in the Chinese couples revealed rarer mutations at -29 and an ATG-AGG base substitution at the initiation codon for translation. In the Malay couples, genomic sequencing detected mutations at codon 15 (TGG-TAG) and codon 26 (GAG-AAG). We conclude that ARMS with its direct detection of amplified products by gel electrophoresis provides an accurate, rapid, and simpler method for our beta-thalassaemia prenatal diagnosis programme in Singapore.

Autoradiography↗

PubMed1994

DNA amplification by the polymerase chain reaction for the rapid diagnosis of tuberculous meningitis. Comparison of protocols involving three mycobacterial DNA sequences, IS6110, 65 kDa antigen, and MPB64.

DNA amplification of three Mycobacterium tuberculosis-specific DNA sequences by the polymerase chain reaction (PCR) were evaluated as a means for rapid diagnosis of tuberculous meningitis (TBM). The DNA sequences amplified were a 123 bp region of the IS6110 insertion elements which occur in multiple copies in the mycobacterial genome, a 240 bp region (nts 460-700) from the MPB 64 protein coding gene, and the 383 bp region of the 65 kDa heat shock protein (HSP) antigen. Twenty-seven cerebrospinal fluid (CSF) specimens were studied. Six were obtained from patients with TBM diagnosed by culture (4/6) or by the patients' response to anti-tuberculous therapy (2/6). The remaining 21 specimens were obtained from patients with febrile seizures (3/21), aseptic meningitis (3/21), septic meningitis (14/21), and cryptococcal meningitis (1/21), and these served as negative controls. Our results indicate that although the protocols involving the 3 DNA sequences were able to detect TB DNA in the 6 TBM specimens, the main drawback was their extreme sensitivity, thus giving rise to false positive results. In particular, the repeat copy sequence, IS6110, and the 65 kDa HSP gave unacceptably large numbers of false positive results (62% and 33%, respectively).

Antigens, Bacterial↗

PubMed1994

Lack of association of the dopamine D3 receptor gene polymorphism (BalI) in Chinese schizophrenic males.

Dopamine receptors have been implicated in the aetiology of schizophrenia and mode of action of antipsychotic drugs. A finding of increased homozygosity at the D3 receptor gene (BalI locus) has recently been reported. We have investigated the distribution of D3 receptor gene polymorphism (BalI) in 137 schizophrenic Chinese males and 125 healthy matched controls. The frequency of the rare allele was 0.30 and 0.31 in the patient and the control series. The distribution of genotypes in the patient series did not deviate significantly from Hardy-Weinberg equilibrium in the present series.

Adult↗

PubMed1994

Interrelationships of serum paraoxonase, serum lipids and apolipoproteins in normal pregnancy. A longitudinal study.

Serum paraoxonase (EC 3.1.1.2) may be implicated in the lipid metabolism. In order to substantiate this view we conducted a longitudinal study of interrelationships of serum paraxonase, lipids and apolipoproteins during pregnancy. Fasting serum levels of paraoxonase, serum lipids (total, HDL and LDL cholesterols, triglycerides) and apolipoproteins (AI, AII and B) were estimated in 91 pregnant women at 28 and 32 weeks of gestation and 6 weeks after delivery, and 40 nonpregnant women. Serum paraoxonase, total HDL and LDL cholesterol levels were significantly higher during pregnancy along with corresponding apolipoprotein (p < 0.001). The most striking increase was seen in serum triglycerides and paraoxonase levels (p < 0.001). Serum paraoxonase levels had a significant correlation with triglycerides (r: 0.45-0.60) and Apo-AII (r: 0.32-0.41) in both pregnant and nonpregnant states (p < 0.001). Moreover, both serum paraoxonase and triglyceride levels at 28 weeks of pregnancy were negatively correlated with birth weight (r: 0.3, p < 0.05), suggesting a possible role of paraoxonase in energy delivery for fetal development derived from maternal hypertriglyceridemia.

Apolipoprotein A-II↗

PubMed1994

Association of factor VII genotype with plasma factor VII activity and antigen levels in healthy Indian adults and interaction with triglycerides.

Plasma factor VII activity (factor VIIc) is one of the independent risk factors for coronary artery disease and is controlled by both genetic and environmental factors. Several studies in healthy Caucasian subjects have revealed an association of a common genetic polymorphism at residue 353 (Arg-->Gln) of the factor VII gene with plasma factor VIIc. We have investigated the influence of this polymorphism (factor VII Arg/Gln353) on fasting plasma factor VIIc and antigen (factor VIIag) levels and its interaction with triglyceride levels in 185 healthy Dravidian Indians of both sexes (128 men, 57 women). The frequency of Gln353 has been found to be significantly higher in Dravidian Indians (0.29; confidence interval, 0.27 to 0.30) than in Caucasians (0.10). The distribution of factor VII Arg/Gln353 genotypes was at Hardy-Weinberg equilibrium. The carriers of the Gln353 allele had significantly lower plasma factor VIIc and factor VIIag in men (P < .05). The factor VII Arg/Gln353 polymorphism explained 13% and 11% of the total variance of plasma factor VIIc and factor VIIag, respectively, in men (P < .001) and 6% and 9% in women (P > .1). The genotype-specific correlation of factor VIIc and factor VIIag with triglyceride levels was stronger in carriers of the Gln353 allele (r = .38 and .41; P < .001) than in Arg353 homozygotes (r = .09 and .27; P = .19 and .005, respectively).

Adult↗

PubMed1994

The diagnosis of tuberculous meningitis using the polymerase chain reaction.

AIM: DNA amplification by the polymerase chain reaction (PCR) was evaluated as a means for rapid diagnosis of tuberculous meningitis (TBM). METHODS: A 240 bp region (nts 460-700) from the MPB 64 protein coding gene specific for Mycobacterium tuberculosis (TB) was selected for amplification. Nineteen clinical samples were studied. Six were obtained from patients with TBM diagnosed by culture (4/6) or by response to therapy (2/6). The remaining 13 samples were obtained from patients with febrile seizu es (8/13), aseptic meningitis (3/13) and septic meningitis (2/13), and these served as negative controls. RESULTS: We detected TB DNA in all the 6 CSF specimens obtained from patients with TBM. PCR alone was sufficient to detect TB DNA in 5 of these 6 samples. However, one sample was positive only when PCR was followed by oligonucleotide hybridisation. In the 2 patients whose CSF were obtained only after commencement of TB therapy, TB cultures were negative but positive on PCR nd oligoprobe labelling. The diagnosis of TBM was confirmed based on their remarkable response to therapy. Twelve of the thirteen negative controls were TB DNA negative. There was one false positive sample, which was thought to be due to TB DNA contamination. CONCLUSION: Taken together, our results indicate that DNA amplification using PCR, followed by oligonucleotide hybridisation offers a rapid (5 working days) means of diagnosis of TBM, provided care is taken to ensure that cross contamination of DNA samples is avoided.

DNA Primers↗

PubMed1993

Apolipoprotein H polymorphism and serum lipoprotein and apolipoprotein levels in two Asian populations.

The apolipoprotein H (apo H) is a constituent of several lipoprotein particles and, therefore, may play an important role in lipid metabolism. In this study, we have investigated the role of common apo H structural polymorphism in determining serum total cholesterol; high-density lipoprotein cholesterol; triglycerides; and apolipoproteins A-I, A-II, and B in 655 Chinese and 126 Dravidian Indians from Singapore. Serum lipoprotein and apolipoprotein levels were adjusted for significant concomitant variables for age and body mass index, and the quantitative mean values between different apo H genotypes were compared by an analysis of covariance. The distributions of serum lipoprotein and apolipoprotein levels were found to be comparable between the three common apo H genotypes in both ethnic groups, indicating that the apo H polymorphism may not play a significant role in lipid metabolism.

Apolipoproteins↗

PubMed1992

Origin of the Koreans: a population genetic study.

A population genetic study was undertaken to investigate the origin of Koreans. Thirteen polymorphic and 7 monomorphic blood genetic markers (serum proteins and red cell enzymes) were studied in a group of 437 Koreans. Genetic distance analyses by both cluster and principal components models were performed between Koreans and eight other populations (Koreans in China, Japanese, Han Chinese, Mongolians, Zhuangs, Malays, Javanese, and Soviet Asians) on the basis of 47 alleles controlled by 15 polymorphic loci. A more detailed analysis using 65 alleles at 19 polymorphic loci was performed on six populations. Both analyses demonstrated genetic evidence of the origin of Koreans from the central Asian Mongolians. Further, the Koreans are more closely related to the Japanese and quite distant from the Chinese. The above evidence of the origin of Koreans fits well with the ethnohistoric account of the origin of Koreans and the Korean language. The minority Koreans in China also maintained their genetic identity.

Alleles↗

PubMed1992

Apolipoprotein B-gene DNA polymorphisms (XbaI and EcoRI), serum lipids, and apolipoproteins in healthy Chinese.

The frequency of restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apo B) gene, detected by XbaI and EcoRI, and their influence on serum lipids and apolipoproteins were studied in healthy Chinese of both sexes in Singapore. A total of 221 subjects (150 males, 71 females) were investigated for the XbaI and 159 subjects for the EcoRI polymorphisms, while serum lipids and apolipoprotein levels were available for 196 subjects. The frequency of the X2 allele was found to be significantly lower in the Chinese than that reported in Caucasians from the United Kingdom (0.09 vs. 0.51, P less than 0.001). The haplotype frequencies were also significantly different between the Chinese and Caucasians with a higher frequency of X1R1 in the former compared to the latter (0.85 vs. 0.34, P less than 0.0001). The distribution of RFLP genotypes at both of the restriction sites was at Hardy-Weinberg equilibrium in all groups. The influence of the apo B RFLPs on serum lipids and apolipoprotein levels (apo AI, AII, and B) was studied by both residual and multiple regression analyses considering age, sex, body mass index (BMI), and genotypes as independent variables in all possible combinations. No association was observed between the apo B genotypes and serum lipids or apolipoprotein levels except for high density lipoprotein cholesterol (HDLC), apo AI and AII, with the X2 being associated with significantly lower levels of HDLC as well as apo AI and AII, the effect being stronger in males. These data raise the possibility that the mechanism of reported association between apo B polymorphism and coronary artery disease may be through effects on HDLC.

Adult↗

PubMed1992

Deletion analysis of DMD/BMD children in Singapore using multiplex polymerase chain reaction (PCR) technique.

Twenty-three children suffering from Duchenne/Becker muscular dystrophy (DMD/BMD) in Singapore were analysed using the multiplex polymerase chain reaction (PCR) technique. Deletions were found in 14 cases. One rare case of total deletion of all nine exons was observed. This is the first DMD/BMD deletion analysis on South East Asian children. This technique for screening deletions was informative in 61 per cent of the local cases and would be useful for rapid diagnosis of deletion cases of DMD/BMD.

Adolescent↗

PubMed1992

Association of haptoglobin types with serum lipids and apolipoproteins in a Chinese population.

Association of haptoglobin types with serum lipids and apolipoprotein levels was investigated in a healthy Chinese population of both sexes (n = 679) in Singapore. The frequency of Hp1 and Hp2 was found to be 0.30 and 0.70, respectively. The distribution of haptoglobin phenotypes was at Hardy-Weinberg equilibrium in this population. There was an excess of Hp2 in individuals with the upper two quartiles of serum total cholesterol levels compared to those with the lower two quartiles in both sexes (X1(2): 11.84; P less than 0.001). Subjects with Hp 2-2 had significantly higher serum total and LDL cholesterol levels (243.8 +/- 2.83 and 165.9 +/- 2.48 mg/dl) compared to those in other haptoglobin types (230.7 +/- 2.58 and 154.9 +/- 2.49 mg/dl), respectively (P less than 0.001 and 0.002) after adjustments for age, sex and BMI. No other lipid (HDL cholesterol and triglyceride) and apolipoprotein (apo A-I, A-II and B) traits were associated with haptoglobin types. ANOVA statistics using age, sex and BMI as covariates showed that 1.8% of total variability of serum total cholesterol and 2.1% of serum LDL cholesterol could be explained by haptoglobin types (P 0.008 and 0.003, respectively). It is concluded that haptoglobin polymorphism is significantly associated with serum total and LDL cholesterol levels in this Chinese population.

Adolescent↗

PubMed1992

DNA polymorphisms of the apolipoprotein B gene in Chinese coronary artery disease patients.

Five restriction fragment length polymorphisms (RFLP) of the apo B gene and their association with serum lipids and apolipoprotein levels have been studied in 139 Chinese patients with angiographically confirmed CAD (mean age 56.2 +/- 0.8 years) and 154 healthy Chinese subjects (mean 44.0 +/- 1.0 years) of both sexes. The patient group had significantly higher levels of serum total and LDL cholesterol; and apo B (P < 0.001) and lower HDL cholesterol and apo A-I (P < 0.001 and < 0.01, respectively). The frequencies of the rarer alleles of the ins/del, XbaI and EcoRI (but not the PvuII and MspI) polymorphisms were significantly lower in the Chinese compared to those reported in Caucasians. There was no significant difference in allelic frequencies of the signal peptide region (Ins/Del), XbaI, MspI and EcoRI sites of the apo B gene between the patient and control groups. The frequency of the rarer allele of the PvuII RFLP was significantly lower in the CAD patients (P < 0.05) compared to that in the control group (0.05 vs 0.10). None of the DNA polymorphisms was associated with a significant influence on serum lipid and apolipoprotein levels in the patients with coronary artery disease.

Alleles↗

PubMed1992

Influence of apolipoprotein B signal peptide insertion/deletion polymorphism on serum lipids and apolipoproteins in a Chinese population.

Insertion/deletion polymorphism of the apo B gene encoding signal peptide and its influence on serum lipids and apolipoproteins was studied in 269 Chinese of both sexes in Singapore. The frequency of the Del allele was found to be 0.20, which is significantly lower than that in Caucasians (France) (0.34). The distribution of genotypes of ins/del polymorphism was at Hardy-Weinberg equilibrium in this population. There was an excess of individuals with the deletion allele in hypercholesterolemic subjects compared to those with normal cholesterol levels (P less than 0.05). All the lipid and apolipoprotein values were regressed for age, sex and BMI by multiple regression analysis. Individuals with one or two del alleles had significantly higher levels of serum total cholesterol (248.8 +/- 13.0 and 255.4 +/- 20.4 mg/dl, respectively) compared to those in individuals with only the Ins allele (218.4 +/- 7.8 mg/dl) (P less than 0.05). Serum LDL cholesterol level was also significantly higher in individuals with del allele (173.4 +/- 11.7 mg/dl) compared to that in those without the del allele (141.1 +/- 7.4 mg/dl) (P = 0.02). The percentages of sample variance of different lipid traits explained by apo B signal peptide polymorphism were estimated by analysis of variance (ANOVA) with sex, age and BMI as covariates. 2.3% of variability of serum total cholesterol (F = 3.27, P = 0.040) and 2.8% of LDL cholesterol (F = 3.87, P = 0.023) could be explained by the ins/del polymorphism of the apo B signal peptide gene.

Adolescent↗