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Biomedical subjects

S Tan

Publications and source records attributed to S Tan.

At least 109 records · Page 6Linked to original sources
PubMed1998

The efficacy and safety of mivacurium in children in Singapore.

AIM: The aim of this study was to evaluate the clinical use of mivacurium, a short-acting, non-depolarising muscle relaxant, in the paediatric population in Singapore. METHODS: Twenty children between the ages of 2 and 12 years were given mivacurium to maintain neuromuscular blockade during nitrous oxide-halothane anaesthesia. Reversal from neuromuscular blockade was spontaneous. The onset, ease of intubation after different doses of mivacurium, and the ease of reversal were evaluated. RESULTS: Different intubating doses of mivacurium did not result in significantly different times of onset. The mean recovery index (25% to 75% recovery) was 4.1 minutes. There were no adverse reactions. CONCLUSIONS: Mivacurium provided rapid and efficacious onset of neuromuscular blockade in the local paediatric population. Rapid spontaneous recovery obviated the need for reversal agents.

Child↗
PubMed1997

Promoter escape by RNA polymerase II. Formation of an escape-competent transcriptional intermediate is a prerequisite for exit of polymerase from the promoter.

Shortly after initiating promoter-specific transcription in vitro, mammalian RNA polymerase II becomes highly susceptible to arrest in a promoter-proximal region 9-13 base pairs downstream of the transcriptional start site (Dvir, A., Conaway, R. C., and Conaway, J. W. (1996) J. Biol. Chem. 271, 23352-23356). Arrest by polymerase in this region is suppressed by TFIIH in an ATP-dependent reaction (Dvir, A., Conaway, R. C., and Conaway, J. W. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 9006-9010). In this report, we present evidence that, in addition to TFIIH and an ATP cofactor, efficient transcription by RNA polymerase II through this promoter-proximal region requires formation of an "escape-competent" transcriptional intermediate. Formation of this intermediate requires template DNA 40-50 base pairs downstream of the transcriptional start site. This requirement for downstream DNA is transient, since template DNA downstream of +40 is dispensable for assembly of the preinitiation complex, for initiation and synthesis of the first 10-12 phosphodiester bonds of nascent transcripts and for further extension of transcripts longer than approximately 14 nucleotides. Thus, promoter escape requires that the RNA polymerase II transcription complex undergoes a critical structural transition, likely driven by interaction of one or more components of the transcriptional machinery with template DNA 40-50 base pairs downstream of the transcriptional start site.

Adenosine Triphosphate↗
PubMed1997

Association between beta 2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics.

BACKGROUND: In-vitro studies have suggested that polymorphisms of the beta 2-adrenoceptor may influence the desensitisation induced by beta 2-agonists. We investigated the influence of beta 2-AR polymorphism on the development of bronchodilator desensitisation in asthma patients. METHODS: We carried out an analysis of 22 moderately severe stable asthmatics, mean age 38 years, FEV1 63% of predicted and FEF25-75 38% of predicted, who received a median inhaled corticosteroid dose of 1000 micrograms/day. Patients were randomly assigned inhaled placebo or inhaled formoterol 24 micrograms bid for 4 weeks each in a crossover study. Bronchodilator dose-response curves were made at the end of each treatment period by use of cumulative doses of formoterol (6-108 micrograms) with FEV1 and FEF25-75 measured 30 min after each dose, and up to 6 h after the last dose. We calculated the degree of bronchodilator desensitisation by comparing the dose-response (for maximum and 6 h) after placebo with that after formoterol, and expressed this degree as a percentage of placebo response. Patients were divided into groups according to genotype at codon 16: homozygous Arg 16 (n = 4), heterozygous Arg 16/Gly 16 (n = 8), and homozygous Gly 16 (n = 10). At codon 27: homozygous Gln 27 (n = 5), heterozygous Gln 27/Glu 27 (n = 11), and homozygous Glu 27 (n = 6). FINDINGS: We found a significantly (p < 0.05) greater degree of bronchodilator desensitisation with homozygous Gly 16 than with homozygous Arg 16 for maximal FEV1 response: -8% (Arg 16) vs 46% (Gly 16); and for maximal FEF25-75 response: -32% (Arg 16) vs 74% (Gly 16; 95% CI 15-92% and 49-164%, respectively). Bronchodilator responses at 6 h were also significantly (p < 0.05) different for FEV1 and FEF25-75 when Arg 16 and Gly 16 were compared and values for heterozygous Arg 16/Gly 16 were intermediate. There was significantly greater desensitisation with Glu 27 than with Gln 27 for maximal FEF25-75 response: -7% (Gln 27) vs 68% (Glu 27), p = 0.05; and for 6 h FEF25-75 response: 43% (Gln 27) vs 93% (Glu 27), p < 0.05 (95% CI 2-147% and 5-94%, respectively). All patients who were homozygous Glu 27 were also homozygous Gly 16. INTERPRETATION: We have found preliminary evidence that beta 2-adrenoceptor polymorphism is associated with altered beta 2-adrenoceptor expression in asthma patients. The homozygous Gly-16 form was significantly more prone to bronchodilator desensitisation than Arg 16, with the influence of Gly 16 dominating over any putative protective effects of Glu 27.

Administration, Inhalation↗
PubMed1997

The role of protein phosphorylation in beta amyloid toxicity.

Recent evidence suggests that amyloid beta protein (A beta) mediates the neurotoxicity observed in Alzheimer's disease (AD). Little is known, however, about the cytotoxic pathway leading to nerve cell death. Using a rat brain cell line which is sensitive to A beta, it is shown that a 50-60 kDa protein becomes more phosphorylated when cells are exposed to A beta. Several kinase and phosphatase inhibitors block both the increase in phosphorylation of the 50-60 kDa protein and A beta toxicity. In contrast, a tyrosine kinase inhibitor blocks toxicity at a step which is distinct from the phosphorylation of this protein. A beta also causes a general increase in overall phosphatase activity. It is therefore likely that a protein phosphorylation cascade is involved in A beta toxicity.

Amyloid beta-Peptides↗
PubMed1997

Comparative topical anaesthesia of EMLA and liposome-encapsulated tetracaine.

BACKGROUND: The eutectic mixture of local anaesthetics (EMLA) provides effective topical anaesthesia after a minimum of 60 to 90 min application. Since liposome-encapsulated tetracaine (LET) can provide rapid dermal penetration, the goal of this study was to compare the local anaesthetic effects of EMLA and LET in human volunteers after 60 min application. METHODS: After obtaining institutional approval and informed consent, healthy volunteers were recruited in a double blind, crossover, randomized trial. The study creams (0.5 ml EMLA and 0.5 ml LET 5%) were applied randomly to opposite arms for 60 min. The discomfort of i.v. catheterization was assessed using a visual analogue pain score (VAS). Cutaneous side effects of the creams were recorded. RESULTS: Sixty-one subjects were studied. Twenty-one were excluded because of technical difficulties. Forty subjects completed the study and were included in the data analysis. The mean ( +/- SD) VAS was lower for LET than for EMLA (10.9 +/- 9.0 mm vs 22.7 +/- 17.1 mm, P < 0.001). Erythema secondary to vasodilatation occurred more frequent in the LET group than in the EMLA group (33 vs 3, P < 0.001). One subject with a history of atopy developed a rash at the LET application site. CONCLUSION: Liposome-encapsulated tetracaine can provide a more effective topical anaesthesia than EMLA for intravenous catheterization after 60 min application. Clinical evaluations are necessary to determine the efficacy and safety of LET in providing topical anaesthesia for various invasive percutaneous procedures in other patient populations.

Administration, Topical↗
PubMed1997

Evaluation of an aroA mutant Salmonella typhimurium vaccine in chickens using modified semisolid Rappaport Vassiliadis medium to monitor faecal shedding.

In groups of chickens vaccinated orally or intramuscularly with a live aroA mutant Salmonella typhimurium vaccine strain and then experimentally inoculated with 10(8) CFU of wild type S. typhimurium or 10(9) CFU of S. enteritidis, faecal shedding of the vaccine and wild type strains was monitored by the buffered peptone water-modified semisolid Rappaport Vassiliadis medium method, which detected less than 10(2) CFU per gram of faeces. The vaccine strain was shed in the faeces for up to 26 days. Vaccination failed to reduce the faecal shedding of wild type S. typhimurium or S. enteritidis. The variation in the shedding patterns of chickens within each group was greater than between treatment groups.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1997

Comparison of an LPS-specific competitive ELISA with a motility enrichment culture method (MSRV) for detection of Salmonella typhimurium and S. enteritidis in chickens.

We report here evaluation of a competitive enzyme-linked immunosorbent assay (c-ELISA) for detection of Salmonella spp. in chicken organs and faeces. The c-ELISA used a monoclonal antibody (MAb), specific for a genus-specific epitope of the outer core oligosaccharide of salmonellae. Salmonella lipopolysaccharide (LPS) in samples competed with Salmonella LPS coated on microtitre plates, for binding to the MAb. Competition reduced binding of the MAb to the LPS on the plate and of the secondary antibody to the MAb hence reducing the chromogenic signal. Stable coating and minimal false positive were achieved by conjugating LPS to poly-L-lysine. The c-ELISA was compared with motility enrichment culture using modified semisolid Rappaport Vassiliadis (MSRV) medium, which detected less than 10(2) CFU/g, and did not allow migration of non-salmonella species. The c-ELISA detected 10(6) CFU of enriched culture or 10(2)-10(3) CFU of Salmonella/g of faeces. Its limit of detection was thus higher than that of MSRV culture and it had a sensitivity of 92.9% and a specificity of 96.7%.

Animals↗
PubMed1997

LhcaR1 of the red alga Porphyridium cruentum encodes a polypeptide of the LHCI complex with seven potential chlorophyll a-binding residues that are conserved in most LHCs.

The accessory light-harvesting polypeptides associated with photosystem I (LHCI) in Porphyridium cruentum bind chlorophyll a, zeaxanthin and beta-carotene. A cDNA library of P. cruentum was screened with an antiserum specific to the LHCI polypeptides, and an 0.9 kb fragment was identified as coding for an LHCI polypeptide. This cDNA, which we named LhcaR1, has an open reading frame encoding 222 amino acid residues including a putative transit peptide of 28 amino acids. Hydropathy analysis suggests that there are three transmembrane helices in the mature polypeptide. Each of the amino acid residues that bind chlorophyll (six residues) and serve in stabilizing the helices in higher-plant LHCs are conserved in helices 1 and 3 of P. cruentum LhcaR1. The N-terminal flanking regions of these two helices also show high sequence conservation with other LHCs. Helix 2 contains a seventh putative chlorophyll-binding site, but resembles helix 2 of higher-plant LHCs to a lesser degree. A sequence motif of 11 residues found near the N-terminus and in each of the three helices suggests the possibility that the red algal LhcaR1 derives from a gene duplication. Polypeptides of the expected molecular weight in six other red algae (Achrochaetium, Bangia, Callithamnion, Cyanidium, Polysiphonia, Spermothamnion) were recognized by the antiserum to P. cruentum LHCI, indicating a wide distribution of LHCI in rhodophytes.

Algal Proteins↗
PubMed1997

Cognitive testing of elderly Chinese people in Singapore: influence of education and age on normative scores.

AIM: to establish age- and education-adjusted mean psychometric test scores of cognitively normal elderly Chinese people in Singapore. METHOD: 155 community-living, cognitively intact elderly Chinese subjects, stratified according to age and education, were selected from the membership lists of senior citizens' clubs and were administered a neuropsychological assessment battery. The mean test scores were then analysed for correlations with demographic characteristics. RESULTS: only education and age were independent variables; gender and language spoken were strongly correlated with education by the chi2 method (P < 10[-5]). Subsequent statistical analysis of education and age on the psychological test scores by the general linear model procedure enabled the formulation of a table of age- and education-adjusted normative cognitive scores. CONCLUSION: the derivation of age- and education-adjusted normative scores of a selected neuropsychological assessment battery on elderly Chinese people enables a more accurate diagnosis of dementia to be made and may facilitate better international comparisons of this condition. As our subjects are representative of many others from China, these results may serve not only as a local, but also as a regional, reference source.

Age Factors↗
PubMed1997

Halothane and xanthine oxidase increase hepatocellular enzyme release and circulating lactate after ischemia-reperfusion in rabbits.

BACKGROUND: Multiple-organ injury often occurs after aortic occlusion-reperfusion. Oxidants derived from xanthine oxidase have been implicated as a source of injury after aortic occlusion-reperfusion. Halogenated anesthetics modify oxidant-mediated injury. The current study determined if halothane modifies hepatocellular enzyme release (e.g., alanine aminotransferase) and circulating lactate after aortic occlusion-reperfusion. METHODS: Rabbits were randomly assigned to one of four groups that underwent 40 min of thoracic aortic occlusion and 2 h of reperfusion: Two groups were given either halothane or fentanyl plus droperidol anesthesia and two groups were given either anesthetic and sodium tungstate (xanthine oxidase inactivator). Each of the four groups was then matched with a similarly treated group that did not undergo aortic occlusion. RESULTS: Halothane anesthesia was associated with significantly (P < 0.05) increased release of alanine aminotransferase (34 +/- 9 U/l at baseline and 539 +/- 370 U/l at 120 min of reperfusion; mean +/- SD) and increased plasma lactate concentrations (2.8 +/- 2.0 mM at baseline and 12.1 +/- 9.7 mM at 120 min of reperfusion) after aortic occlusion-reperfusion compared with fentanyl plus droperidol anesthesia (alanine aminotransferase, 33 +/- 12 U/l and 148 +/- 109 U/l; lactate, 3.4 +/- 2.0 mM and 3.8 +/- 1.2 mM at baseline and 120 min of reperfusion, respectively). Inactivation of xanthine oxidase significantly decreased the release of hepatocellular enzymes (P < 0.05) and decreased circulating lactate in animals anesthetized with halothane after aortic occlusion-reperfusion. CONCLUSIONS: Halothane increased hepatocellular enzyme release and circulating lactate after aortic occlusion-reperfusion compared with fentanyl plus droperidol anesthesia. Xanthine oxidase activity inactivation also decreased hepatocellular enzyme activity release during reperfusion. These findings justify further investigations to determine if halogenated anesthetics modify tissue injury in clinical settings involving oxidant stress.

Anesthetics, Inhalation↗
PubMed1997

Xanthine oxidase mediates myocardial injury after hepatoenteric ischemia-reperfusion.

OBJECTIVES: To determine if myocardial injury results from hepatoenteric ischemia-reperfusion. We also proposed to determine if this remote heart injury is mediated by a xanthine oxidase-dependent mechanism. DESIGN: Randomized, controlled animal study. SETTING: University-based animal research facility. SUBJECTS: Thirty-six New Zealand white male rabbits, weighing 1.8 to 3 kg. INTERVENTIONS: Anesthetized rabbits were randomly assigned to one of four groups (n = 9 per group): a) a sham-operated group; b) a sham-operated group pretreated with sodium tungstate (xanthine oxidase inactivator); c) an aorta occlusion group; and d) an aorta occlusion group pretreated with sodium tungstate. Descending thoracic aorta occlusion was maintained for 40 mins with a 4-Fr Fogarty embolectomy catheter, followed by 2 hrs of reperfusion. MEASUREMENTS AND MAIN RESULTS: Myocardial injury, manifested by increased circulating creatine kinase-MB fraction activity, was significantly associated with aortic occlusion and reperfusion (p < .05). Sodium tungstate pretreatment significantly (p < .05) reduced circulating and myocardial xanthine oxidase activity. Xanthine oxidase inactivation by sodium tungstate significantly decreased circulating creatine kinase-MB fraction activity after hepatoenteric ischemia-reperfusion (p < .05). Finally, circulating creatine kinase-MB fraction activity was significantly associated with circulating xanthine oxidase activity (r2 = .85; p < .001). CONCLUSIONS: We conclude that remote myocardial injury is caused by hepatoenteric ischemia-reperfusion. The pathoetiology of this myocardial injury involves a xanthine oxidase-dependent mechanism.

Animals↗
PubMed1997

Hextend (hetastarch solution) decreases multiple organ injury and xanthine oxidase release after hepatoenteric ischemia-reperfusion in rabbits.

OBJECTIVE: We hypothesized that multiple organ injury and concentrations of xanthine oxidase (an oxidant-generating enzyme released after hepatoenteric ischemia) would be decreased by the administration of a bolus of a colloid solution at reperfusion. DESIGN: Randomized, masked, controlled animal study. SETTING: University-based animal research facility. SUBJECTS: Fifty-four New Zealand white male rabbits, weighing 2 to 3 kg. INTERVENTIONS: Anesthetized rabbits were assigned to either the hepatoenteric ischemia-reperfusion group (n = 27) or the sham-operated group (n = 27). Hepatoenteric ischemia was maintained for 40 mins with a balloon catheter in the thoracic aorta, followed by 3 hrs of reperfusion. Each group was randomly administered a bolus of one of three fluids at the beginning of reperfusion: Hextend (hetastarch solution); 5% human albumin; or lactated Ringer's solution. The investigators were masked as to the identity of the fluid administered. MEASUREMENTS AND MAIN RESULTS: Multiple organ injury was assessed by the release of lactate dehydrogenase activity into the plasma and by indices of gastric and pulmonary injury. Circulating lactate dehydrogenase activity was significantly greater (p < .001) in animals receiving lactated Ringer's solution than in rabbits receiving either colloid solution. Gastric injury (tissue edema, Histologic injury Score) was significantly decreased (p < .01) by administration of both colloid solutions. Lung injury (bronchoalveolar lavage lactate dehydrogenase activity) was significantly decreased (p < .05) by the hetastarch solution administration. The hetastarch solution administration resulted in 50% less xanthine oxidase activity release during reperfusion compared with albumin or lactated Ringer's solution administration (p < .001). CONCLUSION: We conclude that multiple organ injury and xanthine oxidase release after hepatoenteric ischemia-reperfusion are decreased by colloid administration.

Animals↗
PubMed1997

Cognitive testing of elderly Chinese from selected community clubs in Singapore.

The aim of this study was to describe the psychometric performance of cognitively normal elderly Chinese on selected psychological tests. One hundred and fifty-five community-living, cognitively intact elderly Chinese, stratified according to age and gender were administered a selected neuropsychological assessment battery which comprised the Abbreviated Mental Test (AMT), the Chinese Mini-Mental Status (CMMS), the Short Blessed Test (SBT), the Word-List Immediate Memory (WL-i), the Word-List Delayed Memory (WL-d), the Word-List Recognition Memory (WL-r), the Set Test (ST), the modified Boston Naming Test (BNT), the Constructional Praxis Test (CPT), the Block Design Test (BDT) and the Object Assembly Test (OAT). The local median scores (ranges) of the above tests were as follows-AMT: 9 (6-10); CMMS: 25 (16-28); SBT: 2 (0-10); WL-i: 17 (8-27); WL-d: 5 (0-10); WL-r: 9 (1-10); ST: 13 (6-25); BNT: 14 (10-15); CPT: 1 (0-3); BDT: 19 (0-42); OAT: 20 (3-33). These results can assist in the clinical identification of cognitive abnormalities amongst the elderly Chinese in Singapore. Future work will attempt to adjust these overall scores for variables such as the subjects' education and age.

Aged↗
PubMed1997

[Effect of human recombinant gamma-interferon on proliferative activity of human laryngeal cancer cell lines].

The effect of human on PCNA expressions of HEP-2 lines was investigated using LSAB (Labelled streptacidin biotin method) with monoclonal antibody Ki-67 (anti-PCNA). The results showed that the PCNA expression which reflects the proliferative activity of cells was dependent on dose of rhu-IFN-gamma in HEP-2 cell lines. Thus, our data suggest that rhu-IFN-gamma might be useful in the treatment of laryngeal cancer because it provides effective cytostatic.

Dose-Response Relationship, Drug↗
PubMed1996

Molecular and pharmacological characterization of native cortical gamma-aminobutyric acidA receptors containing both alpha1 and alpha3 subunits.

We have investigated the existence, molecular composition, and benzodiazepine binding properties of native cortical alpha1-alpha3 gamma-aminobutyric acidA (GABAA) receptors using subunit-specific antibodies. The co-existence of alpha1 and alpha3 subunits in native GABAA receptors was demonstrated by immunoblot analysis of the anti-alpha1- or anti-alpha3-immunopurified receptors and by immunoprecipitation experiments of the [3H]zolpidem binding activity. Furthermore, immunodepletion experiments indicated that the alpha1-alpha3 GABAA receptors represented 54.7 +/- 5.0 and 23.6 +/- 3.3% of the alpha3 and alpha1 populations, respectively. Therefore, alpha1 and alpha3 subunits are associated in the same native GABAA receptor complex, but, on the other hand, these alpha1-alpha3 GABAA receptors from the cortex constitute a large proportion of the total alpha3 population and a relatively minor component of the alpha1 population. The pharmacological analysis of the alpha1- or alpha3-immunopurified receptors demonstrated the presence of two different benzodiazepine binding sites in each receptor population with high (type I binding sites) and low (type II binding sites) affinities for zolpidem and Cl 218,872. These results indicate the existence of native GABAA receptors possessing both alpha1 and alpha3 subunits, with alpha1 and alpha3 subunits expressing their characteristic benzodiazepine pharmacology. The molecular characterization of the anti-alpha1-anti-alpha3 double-immunopurified receptors demonstrated the presence of stoichiometric amounts of alpha1 and alpha3 subunits, associated with beta2/3, and gamma2 subunits. The pharmacological analysis of alpha1-alpha3 GABAA receptors demonstrated that, despite the fact that each alpha subunit retained its benzodiazepine binding properties, the relative proportion between type I and II binding sites or between 51- and 59-61-kDa [3H]Ro15-4513-photolabeled peptides was 70:30. Therefore, the alpha1 subunit is pharmacologically predominant over the alpha3 subunit. These results indicate the existence of active and nonactive alpha subunits in the native alpha1-alpha3 GABAA receptors from rat cortex.

Amino Acid Sequence↗
PubMed1996

Tyrosinase-catalyzed oxidation of 3,4-dihydroxyphenylglycine.

The oxidation chemistry of dopa in relation to melanin biosynthesis has been extensively studied. However, the oxidation of its lower homolog viz., 3,4-dihydroxyphenylglycine has not been described. Using 3,4-dimethoxybenzaldehyde as the starting material, the chemical synthesis of 3,4-dihydroxyphenylglycine was accomplished by Strecker's synthesis and demethylation reactions. Tyrosinase readily oxidized this unusual amino acid to the expected quinone. The glycyl-o-benzoquinone thus formed was highly unstable like its higher analog, dopaquinone. However, unlike its counterpart, it failed to exhibit intramolecular cyclization reaction. Rather, glycyl-o-benzoquinone exhibited facile transformation(s) to ultimately generate 3,4-dihydroxybenzaldehyde as an isolatable product. A probable mechanism involving intermediary formation of unstable quinone methide and carbinolamine intermediates is proposed to account for the novel transformation of glycyl-o-benzoquinone to 3,4-dihydroxybenzaldehyde.

Benzaldehydes↗