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P N Yeoh

Publications and source records attributed to P N Yeoh.

11 recordsLinked to original sources
PubMed1998

Detection of mutations and polymorphism of N-acetyltransferase 1 gene in Indian, Malay and Chinese populations.

The xenobiotic metabolizing enzymes N-acetyltransferases (NATs) are important for the biotransformation and/or bioactivation of drugs and carcinogens. NATs are coded for in humans by two distinct genes, designated NAT1 and NAT2. NAT1, which was originally thought to be monomorphic, was recently reported to exhibit variation in human populations. Recent studies suggested that a genetic polymorphism of NAT1 may be associated with colorectal cancer risk. The distributions of NAT1 allele and genotype frequencies in unrelated individuals among Indian (n = 140), Malay (n = 122) and Chinese (n = 181) populations in Singapore were characterized by polymerase chain reaction-restriction fragment length polymorphism and allele-specific-polymerase chain reaction. The allelic frequencies of NAT1*3, NAT1*4, NAT1*10 and NAT1*11 among Indians were 0.3, 0.51, 0.17 and 0.02, respectively. The corresponding NAT1 allelic frequencies in Malays were 0.29, 0.30, 0.39 and 0.02, respectively, and were similar to those in Chinese in the region. The allelic frequencies of NAT1*3, NAT1*4, NAT1*10 and NAT1*11 among Chinese were 0.33, 0.35, 0.30 and 0.02, respectively. These findings are of importance for the determination of cancer risk in these populations. In addition, nucleotide changes at positions 350-351 (GG to CC) and 497-499 (GGG to CCC) of the NAT1 gene were not found in the alleles of the populations studied.

Acetyltransferases↗
PubMed1995

Frequency of mutant CYP1A1, NAT2 and GSTM1 alleles in normal Indians and Malays.

Several xenobiotic metabolizing enzymes, including CYP1A1, NAT2 and GSTM1, are subject to genetic polymorphisms. Because these enzymes are important for the detoxification and/or bioactivation of drugs and carcinogens, these polymorphisms have important implications in therapeutics and cancer susceptibility. The distributions of CYP1A1, NAT2 and GSTM1 genotype frequencies in unrelated individuals of the Indian (n = 139) and Malay (n = 146) populations were characterized by the polymerase chain reaction. The respective allelic frequencies of wild-type and mutant alleles of CYP1A1 were 0.82 and 0.18 for the Indians, and 0.69 and 0.31 for the Malays. The frequencies of wild-type, M1, M2 and M3 of NAT2 among Indians were 0.44, 0.20, 0.32 and 0.04 respectively. The corresponding NAT2 allelic frequencies in Malays were 0.41, 0.12, 0.38 and 0.09. The GSTM1*A allele could not be amplified in 33.1% of Indians and 61.6% of Malays. At least one GSTM1*B allele was detected in 7.2% and 7.5% of the respective populations. The allelic frequencies of CYP1A1, NAT2 and GSTM1 among Malays are similar to previously reported frequencies among Chinese in the region. These findings will be of importance in the determination of cancer risks in these populations.

Alleles↗
PubMed1995

Glutathione S transferase-theta (GSTT1) genetic polymorphism among Chinese, Malays and Indians in Singapore.

Glutathione S-transferase-theta (GSTT1) is subject to a genetic polymorphism where approximately 50% of a Caucasian population are homozygous for the null allele. Because of the possible association of the polymorphism with increased cancer risk in individuals, we genotyped by polymerase chain reaction 187 normal Chinese, 167 normal Malays and 152 normal Indians from Singapore and Malaysia. The proportion of Chinese, Malays and Indians with the null genotype were 58%, 38% and 16% respectively and mirrored previously reported frequencies of the GSTM1 null genotype in these populations. The frequency of the combined GSTM1 and GSTT1 null genotypes among Chinese, Malays and Indians were 37%, 22% and 5% respectively. The similarity with predicted frequencies indicated no interaction between the two genetic polymorphisms.

Adolescent↗
PubMed1981

Comparative assessment of the anticonvulsant activity of some benzodiazepines, phenobarbitone and diphenylhydantoin against maximal electroshock seizures in rats: a time-distribution study.

The anticonvulsant activity of three benzodiazepines (BZDP) and two standard antiepileptic drugs were investigated comparatively against maximal electroshock seizures in rats in a time-distribution study. While phenobarbitone (PHB) and diphenylhydantoin (DPH) gave marked to moderate protection (100%-67%) against tonic seizures up to 6-7 h post-treatment, the BZDP provided significant protection (100%-60%) only up to 1.5 h, with clonazepam being the strongest and diazepam the weakest. Clonic seizures occurred in all treatment groups, whether tonic seizures preceded them or not, but their duration was longer in the DPH and PHB groups than in the BZDP groups. Total seizure durations were often significantly reduced in the BZDP groups, notably with clonazepam, whereas it was invariably longer in the DPH and PHB groups when compared with the vehicle treated controls. The BZDP treated rats generally required longer time to recover from postictal coma, the effect being dose-related. the DPH and PHB treated rats needed longer recovery time when the treatment-test interval was 18-20 h.

Animals↗
PubMed1981

Chiriquitoxin, a new tool for mapping ionic channels.

Chiriquitoxin is a new natural analog of tetrodotoxin in which the -CH2OH group on C6 has been replaced with a yet unidentified group consisting of 104 mass units. It is unique in being the only known stable analog to be equally potent as tetrodotoxin in blocking the sodium channel. It additionally interferes with the delayed rectifier (potassium) channel. In frog skeletal muscle, it significantly reduced the outward current while abolishing the inward current. It also slows the fast repolarization of the action potential and obliterates the voltage response characteristic of delayed rectification to large outward currents. It completes the tetrodotoxin for the same membrane binding site, thereby suggesting that the same molecule interferes with both the sodium and the potassium channels. A new working hypothesis is proposed in which tetrodotoxin and chiriquitoxin are postulated to bind to a membrane receptor located in the outside surface of the muscle fiber membrane. From the structure of tetrodotoxin and a presumed structure of chiriquitoxin, the Na+ and K+ channels have been estimated to be separated from each other by not less than 5 A nor much more than 15 A.

Amphibian Venoms↗
PubMed1977

The temporal dimensions of anticonvulsant action of some newer benzodiazepines against metrazol induced seizures in mice and rats.

In a time-distribution study, the anticonvulsant effects of four benzodiazepine compounds were compared with those of three standard antiepileptics against metrazol-induced seizures in mice and rats. Ethosuximide and trimethadione had the shortest duration of action in mice, but protected the rats up to 6 hr. Phenobarbitone, diazepam, flurazepam and nitrazepam protected the mice up to 12 hr, but the rats were effectively protected only up to 3-4 hr. Clonazepam, the most potent and effective agent, protected the mice from clonic-tonic seizures up to 18-20 hr and the rats up to 6-7 hr. Comparison of the PD50 from clonic seizure at the peak-effect hours revealed that the benzodiazepines were 16 to 96 times more potent than phenobarbitone on a molar basis, while phenobarbitone itself was 12 to 26 times more potent than ethosuximide and trimethadione. Tonic seizures and mortality were largely suppressed by all drugs until 18-20 hr in mice and 6-7 hr in rats. Seizure latency and mortality patterns varied from drug to drug but not in a dose-dependent manner.

Animals↗