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Biomedical subjects

S Tan

Publications and source records attributed to S Tan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit.

Promoter-specific recruitment of histone acetyltransferase activity is often critical for transcriptional activation. We present a detailed study of the interaction between the histone acetyltransferase complexes SAGA and NuA4, and transcription activators. We demonstrate by affinity chromatography and photo-cross-linking label transfer that acidic activators directly interact with Tra1p, a shared subunit of SAGA and NuA4. Mutations within the COOH-terminus of Tra1p disrupted its interaction with activators and resulted in gene-specific transcriptional defects that correlated with lowered promoter-specific histone acetylation. These data demonstrate that the essential Tra1 protein serves as a common target for activators in both SAGA and NuA4 acetyltransferases.

Acetylation↗
PubMed2001

Hypoxia-ischemia in fetal rabbit brain increases reactive nitrogen species production: quantitative estimation of nitrotyrosine.

Reactive nitrogen species (RNS) cause nitration of protein-bound tyrosine that is used as biomarker for detection. We hypothesized that RNS are formed in fetal rabbit brain following acute placental insufficiency. Near-term pregnant rabbits were randomized to either repetitive uterine ischemia or no ischemia, and fetal brains obtained. Only one electrochemical HPLC method (of three tested) was successful in detecting brain nitrotyrosine. Protein nitrotyrosine was significantly increased following cumulative 40 min ischemia and 20 min reperfusion compared to controls. Repetitive hypoxia-ischemia results in the increased formation of RNS in near-term fetal brains.

Animals↗
PubMed2001

[Horizontal transmission of live attenuated hepatitis A vaccine virus].

OBJECTIVE: To investigate the horizontal transmission of virus after inoculation with live attenuated hepatitis A vaccine. METHODS: One hundred and ninety nine children aged 4 approximately 7 years without anti-HAV and with normal ALT level have been screened out at two trial fields in Anning, Kunming and divided into vaccine group (82 children) and contact group (117 children) to observe the horizontal transmission of the live attenuated hepatitis A vaccine virus (H2 strain). Four supernatant specimens of HAV positive fecal suspension derived from individual vaccines and contacts were taken and injected intravenousely into 8 common marmoset (Callithrix jacchus) for detecting the virulence level of HAV. RESULTS: The rates of seroconversion were 97.6% (80/82) for vaccine group 6 weeks after inoculation and 13.7% (16/117) for contact group at the ninth week of observation. The detection rates of fecal HAV were 89.5% (34/38) and 70.7% (53/75), respectively. No liver functional abnormality has been found in either groups. The responses of 8 marmosets separately infected with fecal shedding HAV of 2 vaccines and 2 contacts have been examined with neither elevations of serum liver enzyme nor liver histopathological changes but delay seroconversions as well as low titers of anti-HAV. CONCLUSION: The safety and immunogenicity live attenuated hepatitis A vaccine (H2 strain) were good. The vaccine virus could actively propagate but keep the stability of attenuated characteristics in human bodies, and might result in horizontal transmission but not induce hepatitis A in crowd.

Animals↗
PubMed2001

The in vitro fate of rabbit fetal brain cells after acute in vivo hypoxia.

In the investigation of ischemia-induced brain damage, traditional methods using histopathology estimate brain cell death at a time remote from ischemic insult. These observations fail to take into account endogenous repair processes or ongoing injury cascades like apoptosis. The cells that are injured but not killed initially are the population most amenable to rescue. The hypothesis was that in vivo uterine ischemia-reperfusion would result in more cell death and apoptosis in fetal brain cells cultured in vitro. Near-term, 29 d gestation, pregnant New Zealand White rabbits were subjected to repetitive uterine ischemia for a cumulative time of 40 min ischemia and 20 min reperfusion. Immediately after uterine ischemia, the fetal brains were removed and dissociated into a cell suspension. The ischemic group had more cell death than non-ischemic controls as assessed by Trypan Blue exclusion and propidium iodide (PI) uptake on a flow cytometer. Aliquots of cells were plated and cultured for 24 and 48 hr. The ischemic group had significantly more cell death (propidium iodide) than non-ischemic controls at 24 hr and significantly more apoptosis, as assessed by annexin-V binding in cells at 24 hr and caspase-3 activity at 48 hr. Fewer cells attached to the culture plates at 48 hr in the ischemia group. After uterine ischemia, certain fetal brain cells die immediately, and other cells undergo ongoing damage resulting in necrosis and apoptosis that is manifest later. This method offers insight into the fate of those cells and provides a tool for assessing interventions to decrease cell injury.

Acute Disease↗
PubMed2001

Regulation of antioxidant metabolism by translation initiation factor 2alpha.

Oxidative stress and highly specific decreases in glutathione (GSH) are associated with nerve cell death in Parkinson's disease. Using an experimental nerve cell model for oxidative stress and an expression cloning strategy, a gene involved in oxidative stress-induced programmed cell death was identified which both mediates the cell death program and regulates GSH levels. Two stress-resistant clones were isolated which contain antisense gene fragments of the translation initiation factor (eIF)2alpha and express a low amount of eIF2alpha. Sensitivity is restored when the clones are transfected with full-length eIF2alpha; transfection of wild-type cells with the truncated eIF2alpha gene confers resistance. The phosphorylation of eIF2alpha also results in resistance to oxidative stress. In wild-type cells, oxidative stress results in rapid GSH depletion, a large increase in peroxide levels, and an influx of Ca(2+). In contrast, the resistant clones maintain high GSH levels and show no elevation in peroxides or Ca(2+) when stressed, and the GSH synthetic enzyme gamma-glutamyl cysteine synthetase (gammaGCS) is elevated. The change in gammaGCS is regulated by a translational mechanism. Therefore, eIF2alpha is a critical regulatory factor in the response of nerve cells to oxidative stress and in the control of the major intracellular antioxidant, GSH, and may play a central role in the many neurodegenerative diseases associated with oxidative stress.

Antioxidants↗
PubMed2001

Evidence for joint genetic control of insulin sensitivity and systolic blood pressure in hispanic families with a hypertensive proband.

BACKGROUND: The clustering of hypertension, insulin resistance, and obesity remains unexplained. We tested for genetic and nongenetic influences on the association among these traits in Hispanic families with hypertension. METHODS AND RESULTS: Blood pressure and body mass index (BMI) were measured in 331 members of 73 Hispanic families in which an index case (proband) had hypertension. Insulin sensitivity (S(I)) was measured by euglycemic clamp in 287 probands and their spouses (parents' generation) or their adult offspring. Correlation analysis examined relationships among traits within and between generations. Path analysis estimated genetic and nongenetic contributions to variability in systolic blood pressure (SBP), S(I), and the correlation between them. In the offspring, there was a significant correlation between individuals for each trait, as well as significant correlations within and between individuals for all possible pairs of traits. Between generations, SBP, S(I), and BMI in parents correlated with the same traits in their offspring; BMI in parents correlated with S(I) and SBP in offspring; and S(I) in parents correlated with SBP in offspring. Path analysis estimated that among offspring, genetic effects unrelated to BMI accounted for 60.8% of the variation in SBP, 36.8% of the variation in S(I), and 31.5% of the correlation between SBP and S(I) after adjustment for age and sex. Heritable effects related to BMI accounted for an additional 14.0% of variation in SBP, 26.8% of variation in S(I), and 56.3% of variation in their correlation. CONCLUSIONS: Clustering of hypertension and insulin resistance in Hispanic Americans is accounted for in part by heritable factors both associated with and independent of BMI.

Adolescent↗
PubMed2001

Depression in Singapore: failure to demonstrate an age effect on clinical features.

OBJECTIVES: Studies comparing older and younger depressed patients have variably identified differing and similar clinical feature patterns, an inconsistency requiring clarification and explanation. If influential, age may have a true phenotypic effect or be a secondary influence reflecting depressive sub-type differences. If age is primarily influential, then, after controlling for depressive sub-type differences its effect should impact on clinical features - even in non-western regions. METHODS: We therefore undertook a study in Singapore, comparing 42 elderly and 28 younger patients of a Singapore psychiatric hospital, and with the diagnostic sub-type profile similar across the age-based groups. RESULTS: Despite the elderly group being some 35 years older, both at first episode and when surveyed, and having a distinctly higher rate of physical disorders, few clinical differences were identified. While the elderly group reported a less severe depressed mood and more 'somatic' symptoms, analyses indicated that such differences were accounted for by education and language factors, and were compatible with the view that Chinese subjects historically report depression more 'somatically'. CONCLUSION: We conclude that, in a non-western, largely Chinese sample of depressed patients, few differences in the phenotypic expression of depression were identified, perhaps reflecting similar distributions of depressive sub-types across the groups, an issue which may have muddied interpretation of western studies.

Adolescent↗
PubMed2001

A modular polycistronic expression system for overexpressing protein complexes in Escherichia coli.

To facilitate studies of multicomponent protein complexes, I have developed an Escherichia coli expression system which coexpresses up to four polypeptides from a single plasmid. The modular nature of the system enables efficient subcloning of a gene into each of the 4 cassettes in the polycistronic expression vector. Restriction sites present in the polycistronic expression vector allow both affinity tagged and untagged complexes to be overexpressed. I demonstrate successful use of the expression system for binary and ternary complexes, including the reconstitution of the VHL-elonginC-elonginB complex in E. coli and purification of the complex by affinity and ion-exchange chromatography. This polycistronic expression system should provide an important alternative to in vitro reconstitution of multicomponent complexes.

Base Sequence↗
PubMed2001

Adolescent smoking in Wuhan, China: baseline data from the Wuhan Smoking Prevention Trial.

BACKGROUND: This study reports the prevalence of adolescent smoking in the urban and rural areas of Wuhan, China, the capital of Hubei Province, on the Yangtze River in central China. METHODS: Smoking behavior was examined by age, gender, and urbanicity as part of the Wuhan Smoking Prevention Trial. Subjects included 6994 seventh- to ninth-grade students attending 22 randomly selected schools in urban and rural districts. Outcome measures included lifetime smoking, past-30-day smoking, established smoking (>100 cigarettes in lifetime), and susceptibility to smoking (absence of a firm commitment not to smoke). RESULTS: Lifetime smoking prevalence was 47% among boys and 18% among girls. Past-30-day smoking prevalence was 16% among boys and 4% among girls. Established smoking prevalence was 2% among boys and 0% among girls. The prevalence of susceptibility to smoking was 31% among boys and 10% among girls. Smoking increased significantly with age (p<.0005). Susceptibility was more prevalent in rural areas than in urban areas (p<.05), but there were no urban-rural differences in lifetime, past 30-day smoking, or established smoking. Trend analyses revealed that smoking increased with age more rapidly among boys than among girls (p<.05). Smoking was more prevalent among rural boys than among urban boys, but it was more prevalent among urban girls than among rural girls (p<.05). CONCLUSIONS: Adolescent smoking is a significant public health problem in China. Boys are at particularly high risk, as are girls living in urban areas. Effective smoking prevention programs for adolescents, as well as restrictions on tobacco industry marketing and youth access to tobacco, are needed to prevent tobacco-related morbidity and mortality in China.

Adolescent↗
PubMed2001

A histone fold TAF octamer within the yeast TFIID transcriptional coactivator.

Gene activity in a eukaryotic cell is regulated by accessory factors to RNA polymerase II, which include the general transcription factor complex TFIID, composed of TBP and TBP-associated factors (TAFs). Three TAFs that contain histone fold motifs (yTAF17, yTAF60 and yTAF61) are critical for transcriptional regulation in the yeast Saccharomyces cerevisiae and are found in both TFIID and SAGA, a multicomponent histone acetyltransferase transcriptional coactivator. Although these three TAFs were proposed to assemble into a pseudooctamer complex, we find instead that yTAF17, yTAF60 and yTAF61 form a specific TAF octamer complex with a fourth TAF found in TFIID, yTAF48. We have reconstituted this complex in vitro and established that it is an octamer containing two copies each of the four components. Point mutations within the histone folds disrupt the octamer in vitro, and temperature-sensitive mutations in the histone folds can be specifically suppressed by overexpressing the other TAF octamer components in vivo. Our results indicate that the TAF octamer is similar both in stoichiometry and histone fold interactions to the histone octamer component of chromatin.

Alleles↗
PubMed2001

The role of Bax in glutamate-induced nerve cell death.

The role of the Bax gene product was examined in three forms of cortical nerve cell death in primary cultures. These include spontaneous cell death, oxidative glutamate toxicity, in which exogenous glutamate inhibits cystine uptake resulting in toxic oxidative stress, and ionotropic glutamate receptor-mediated excitotoxicity following a brief exposure to 10 microM glutamate. Primary cortical and hippocampal neuron cultures were established from embryos of Bax -/+ x Bax -/+ matings and the embryos genotyped and assayed for cell death in the three experimental paradigms. Cell death induced by oxidative glutamate toxicity and glutamate-mediated excitotoxicity was not altered in the Bax -/- homozygous knockout animals. In contrast, there was an approximately 50% inhibition of spontaneous cell death. These results suggest that a classical Bax-dependent apoptotic pathway contributes to the spontaneous cell death that takes place when nerve cells are initially exposed to cell culture conditions. A Bax-dependent programmed cell death pathway is not, however, utilized in oxidative glutamate toxicity and NMDA receptor-mediated excitotoxicity following a brief exposure to low concentrations of glutamate.

Animals↗
PubMed2001

Patterns of management of intussusception outside tertiary centres.

BACKGROUND/PURPOSE: Intussusception is a common problem in young children and should have an excellent outcome in expert hands. Many children are treated in district general hospitals (DGH), which do not have specialist paediatric surgeons. The aim of this study was to clarify current patterns of management for such patients. METHODS: The authors conducted a postal survey of DGH consultant paediatricians, radiologists, and general surgeons in a populous region of England. RESULTS: One hundred forty-one (44%) consultants who responded comprised similar proportions of consultants from each specialty. Most respondents (79%) thought that in their location paediatricians should take responsibility for resuscitation of children with suspected intussusception. Two-thirds indicated that abdominal ultrasound scan, either alone or in combination with another modality, was their investigation of choice for confirming the diagnosis. Preferences for contrast medium for radiologic reduction varied; paediatricians favoured air (46%) or saline (28%), surgeons preferred water-soluble contrast (58%), and radiologists preferred to use barium (49%). Fifty-three percent of consultants indicated they would transfer a child with confirmed intussusception to a tertiary centre before attempting reduction, 42% would attempt reduction locally, and 5% would operate locally without attempting radiologic reduction. After failed reduction, a further 23% of consultants would consider transfer, but the remainder would operate locally. Only 13% of paediatricians thought that their surgeons had appropriate facilities and support to operate on intussusception, but 36% of surgeons claimed to be doing so. Most consultants (84%) admitted seeing fewer than 5 cases per year; 98% of surgeons were in this group. Only 16% of consultants (mostly paediatricians) were aware of any written clinical policy for managing paediatric intussusception in their hospital. CONCLUSION: This study shows that the management of paediatric intussusception outside tertiary centres is not uniform or standardised, and that improvements are necessary. J Pediatr Surg 36:312-315.

Case Management↗
PubMed2001

Oxytosis: A novel form of programmed cell death.

Extensive nerve cell death occurs during the development of the central nervous system as well as in episodes of trauma and in neurodegenerative disease. The mechanistic details of how these cells die are poorly understood. Here we describe a unique oxidative stress-induced programmed cell death pathway called oxytosis, and outline pharmacological approaches which interfere with its execution. Oxidative glutamate toxicity, in which exogenous glutamate inhibits cystine uptake through the cystine/glutamate antiporter leading to a depletion of glutathione, is used as an example of oxytosis. It is shown that there is a sequential requirement for de novo macromolecular synthesis, lipoxygenase activation, reactive oxygen species production, and the opening of cGMP-gated channels which allow the influx of extracellular calcium. The translation initiation factor elF2alpha plays a central role in this pathway by regulating the levels of glutathione. Finally, examples are given in which the reduction in glutathione, the production of reactive oxygen species, and calcium influx can be experimentally manipulated to prevent cell death. Data are reviewed which suggest that oxytosis may be involved in nerve cell death associated with nervous system trauma and disease.

Apoptosis↗
PubMed2001

The development of a brief screening measure of emotional distress in children.

We report several studies developing a parent-rated measure of emotional distress for children in Singapore, with the key objectives being to derive a very brief valid measure of global distress. The refined item set comprised behaviourally expressed broad manifestations of emotional distress. Three developmental studies were undertaken, with the first two involving parental ratings on the measure for validation against clinician-rated distress levels, while also testing two rating options for the measure. We established clear comparative advantages to the rating anchors used in the Revised Rutter Scales. High inter-rater agreement was established across parental ratings, with the latter finding supporting objectives for the measure. Paternal scores correlated more strongly than maternal scores with clinician-generated distress scores. Additional properties of the measure were tested in a large community sample of nearly 2,000 Singapore schoolchildren in their last 2 years of primary school, allowing prevalence estimates and mean scores to be derived for each item. Here, girls and boys received identical total scores, scores were also independent of the number of children in the family and of ordinal position, and mothers returned higher scores than fathers.

Adolescent↗
PubMed2001

SL651498: an anxioselective compound with functional selectivity for alpha2- and alpha3-containing gamma-aminobutyric acid(A) (GABA(A)) receptors.

SL651498 [6-fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-1-one] is a novel pyridoindole derivative that displays high affinity for rat native GABA(A) receptors containing alpha(1) (K(i) = 6.8 nM) and alpha2 (K(i) = 12.3 nM) subunits, and weaker affinity for alpha5-containing GABA(A) receptors (K(i) = 117 nM). Studies on recombinant rat GABA(A) receptors confirm these data (K(i), alpha1beta2gamma2 = 17, alpha2beta2gamma2 = 73, alpha5beta3gamma2 = 215 nM) and indicate intermediate affinity for the alpha3beta2gamma2 subtype (K(i) = 80 nM). SL651498 behaves as a full agonist at recombinant rat GABA(A) receptors containing alpha2 and alpha3 subunits and as a partial agonist at recombinant GABA(A) receptors expressing alpha1 and alpha5 subunits. SL651498 elicited anxiolytic-like activity similar to that of diazepam [minimal effective dose (MED): 1-10 mg/kg, i.p.] in three conflict models, in the elevated plus-maze, the light/dark test, and the defense test battery in rats and mice. Results from activity tests and electroencephalogram analysis indicated that SL651498 induced muscle weakness, ataxia, or sedation at doses much higher than those producing anxiolytic-like activity (MED > or = 30 mg/kg, i.p.). Repeated treatment for 10 days with SL651498 (30 mg/kg, i.p., b.i.d.) in mice was not associated with the development of tolerance to its anticonvulsant effects or physical dependence. Furthermore, SL651498 was much less active than diazepam in potentiating the depressant effects of ethanol in mice. The "anxioselective" profile of SL651498 points to a major role for GABA(A) alpha2 subtype in regulating anxiety and suggests that selectively targeting GABA(A) receptor subtypes can lead to drugs with increased clinical specificity.

Animals↗
PubMed2001

186Re-etidronate. Efficacy of palliative radionuclide therapy for painful bone metastases.

Pain palliation with bone-seeking radiopharmaceuticals is an effective treatment modality in patients with advanced metastatic bone cancer. Several studies have shown encouraging clinical results of palliative therapy using 186Re-HEDP, with an overall reported response rate of +/-71% for painful osseous metastasized prostate and breast cancer patients. 186Re-HEDP is a very potential isotope with numerous advantageous characteristics for this purpose. Myelosuppressive toxicity is limited and reversible, which makes repetitive treatment safe. However, individual studies are difficult to compare, and are hampered by the numerous and different methods used to assess clinical response. Standardized clinical response assessment using the objective multi-dimensional pain evaluation model should therefore be implemented.

Bone Neoplasms↗
PubMed2001

[Confirmation of patulous eustachian tube syndrome by Tubo-tymanoaerodynamic graphy].

OBJECTIVE: To compare the advantage of tympanogram, Morimitsu's method and Tubotymanoaerodynamic graphy (TTAG) in the confirmation of patulous eustachian tube syndrome. METHOD: Twenty ears with patulous eustachian tube syndrome diagnosed clinically were selected. The tympanogram, Morimitsu's method and TTAG were examined in these ears and the positive rate was estimated. RESULT: The confirmation of patulous eustachian tube syndrome by tympanogram, Morimitsu's method and TTAG was 5, 12 and 20 ears in 20 ears with patulous eustachian tube syndrome. The positive rate was 25%, 60% and 100% respectively. TTAG also was useful in following-up. CONCLUSION: TTAG is an important method for diagnosis and following-up in patulous eustachian tube syndrome.

Acoustic Impedance Tests↗