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Biomedical subjects

Y T Wang

Publications and source records attributed to Y T Wang.

At least 55 records · Page 3Linked to original sources
PubMed2001

LTP in a culture dish.

The "aging" of populations in the developed world is rapidly altering demographics and presents a number of challenges for science and medicine. Foremost among these challenges is the need to enhance the quality of life for this "aging" majority. Paradoxically, improved prevention and treatment of diseases will only increase the number of individuals who will lose quality of life because of cognitive deficits in learning and memory. Such cognitive deficits are particularly vexing in societies where the ability to deal with information technology has become an increasing necessity. Understanding how the human brain encodes and stores information becomes critical in designing required therapeutic strategies.

Cell Culture Techniques↗
PubMed2001

Cloning and characterization of a novel variant of rat GABA(B)R1 with a truncated C-terminus.

The gamma-aminobutyric acid B receptor (GABA(B)R) belong to the G-protein-coupled receptor superfamily and has been identified as a mediator in the transmission of slow inhibitory neurotransmission in the mammalian central nervous system. Two types of GABA(B)R have been cloned, GABA(B)R1 and R2. GABA(B)R2 is co-expressed with GABA(B)R1 in many brain regions and inwardly rectifying potassium channels are activated by GABA(B)R agonists only upon co-expression of GABA(B)R1 with GABA(B)R2. Several splice variants of GABA(B)R1 receptors have been cloned from rat brain library. Using a rat hippocampal cDNA library, we have isolated a novel cDNA clone of GABA(B) receptor containing an insert of 124 bp between exon 3 and exon 4. This insert occurred between the regions encoding the Sushi domain and leucine binding protein (LBP)-like domain. The insert and subsequent frame shift generated a cDNA that codes for a truncated polypeptide of 239 amino acids lacking the C-terminus. Analysis of the deduced amino acid sequence of the new cDNA clone, termed GABA(B)R1g, showed that it was identical to the first 157 amino acids of GABA(B)R1a, but diverged thereafter. The C-terminal region of GABA(B)R1g contained two cysteine residues. GABA(B)R1g was expressed in both brain and peripheral tissues. Northern blot analysis demonstrated that two transcripts (4.5 kb and 4.0 kb) exist in hippocampus. In addition, studies of hippocampus in developing animals indicated that the expression of GABA(B)R1g is maximal at postnatal day four. GABA(B)R1g could be generated by alternative splicing of the GABA(B)R1 gene.

Alternative Splicing↗
PubMed2001

Gamma-hydroxybutyric acid-induced absence seizures in GluR2 null mutant mice.

In this electrophysiological study, we examined the susceptibility of GluR2 mutant null mice to absence seizures in comparison with wild-type controls. The prodrug of (GHB), gamma-butyrolactone (GBL) was given systemically to induce the absence seizures. We also tested the severity and duration of the seizure activity in this model. The results showed that the latency from GBL administration to onset of seizure was significantly prolonged in GluR2(-/-) mice when compared to GluR2(+/+) mice. The duration of spike-and-wave discharges (SWD) was also significantly decreased in the GluR2(-/-) mice. Ninety minutes following GBL administration, wild-type animals continued to exhibit intermittent SWD bursts while GluR2(-/-) mice had returned to baseline. These data suggest that the GluR2 subunit may be involved in the initiation and maintenance of absence seizures induced by GBL.

Animals↗
PubMed2001

Simultaneous chromium(VI) reduction and phenol degradation in a fixed-film coculture bioreactor: reactor performance.

Simultaneous Cr(VI) reduction and phenol degradation was observed in a fixed-film bioreactor consisting of a coculture of phenol-degrading bacteria, Pseudomonas putida DMP-1, and Cr(VI)-reducing bacteria, Escherichia coli ATCC 33456. Near complete Cr(VI) reduction and phenol degradation was observed during steady-state operation of the reactor under loadings of 5-21 mg Cr(VI) l-1 d-1 and 840-3350 mg phenol l-1 d-1. 2-hydroxymuconic semialdehyde (2HMSA), succinate, and acetate were the detected steady-state organic acid metabolites which accounted for 13-23% of TOC in the effluent. Optimum Cr(VI) reduction rate was observed under a Cr(VI) loading of approximately 26.5 mg Cr(VI) l-1 d-1 just before system overload. System overload was characterized by the increase in effluent Cr(VI) and phenol concentrations. System resilience to Cr(VI) toxicity was demonstrated by rapid recovery of biological activity and reduced effluent Cr(VI) and phenol concentrations after off-loading the system from overloaded conditions.

Biodegradation, Environmental↗
PubMed2001

Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons.

Long-term potentiation (LTP) of excitatory transmission in the hippocampus likely contributes to learning and memory. The mechanisms underlying LTP at these synapses are not well understood, although phosphorylation and redistribution of AMPA receptors may be responsible for this form of synaptic plasticity. We show here that miniature excitatory postsynaptic currents (mEPSCs) in cultured hippocampal neurons reliably demonstrate LTP when postsynaptic NMDA receptors are briefly stimulated with glycine. LTP of these synapses is accompanied by a rapid insertion of native AMPA receptors and by increased clustering of AMPA receptors at the surface of dendritic membranes. Both LTP and glycine-facilitated AMPA receptor insertion are blocked by intracellular tetanus toxin (TeTx), providing evidence that AMPA receptors are inserted into excitatory synapses via a SNARE-dependent exocytosis during LTP.

Animals↗
PubMed2001

Alteration of GLUR2 expression in the rat brain following absence seizures induced by gamma-hydroxybutyric acid.

We explored the involvement of the glutamate receptor subunit B (GluR2) in the mechanism of absence seizures induced by gamma-hydroxybutyric acid (GHB). The expression and distribution of GluR2 protein in rat brain were examined during and after GHB-induced absence seizures. The data indicate that GluR2 protein expression significantly decreases following the onset of absence seizures. The suppression of GluR2 expression was prolonged and it outlasted the duration of the continuous absence seizure activity. The alteration of GluR2 protein levels was accompanied by a re-distribution of GluR2 expression from laminae V to IV in cerebral cortex. We also analyzed the duration and latency of absence seizures induced by GHB 72 h following an initial GHB-induced absence seizure, a time when suppression of GluR2 protein was maximal. The second absence seizure was significantly more prolonged than the first. These data may indicate that the putative down-regulation of GluR2 following GHB-induced absence seizure could have contributed to the potentiation of subsequent seizures in animals. A related hypothesis posed by the data is that down-regulation of GluR2 is involved in the mechanisms of the maintenance of recurrent absence seizure activity once it is initiated and therefore, may contribute to the chronicity of seizures in absence epilepsy.

Animals↗
PubMed2001

Ethnic differences in anthropometry among adult Singaporean Chinese, Malays and Indians, and their effects on lung volumes.

When standing height (StndHt) cannot be assessed, arm span (AS) or sitting height (SitHt) has been used as surrogate variables for prediction of StndHt in adult caucasians and blacks. We examined (1) the relationship between StndHt, AS and SitHt among adult Chinese, Malays and Indians; and (2) whether anthropometry could explain the ethnic differences in lung volumes (as StndHt-adjusted lung volumes are known to differ significantly: Chinese > Malays > Indians). We recruited 1250 consecutive outpatients aged 20-90 years. Prediction equations of StndHt (with AS, SitHt, weight, age as predictors) for each subgroup of race and sex were formulated with multiple linear regressions. Equations with both AS and SitHt as predictors had the best goodness of fit (SEE = 2.37-2.85 cm, adjusted R2 = 0.67-0.87), as compared to equations with either AS (SEE = 3.00-3.91 cm, adjusted R2 = 0.58-0.80) or SitHt alone (SEE = 3.48-4.00 cm, adjusted R2 = 0.45-0.76). GLM general factorial analyses found that age- and weight-adjusted SitHt-to-StndHt ratios differed significantly among Chinese (0.539), Malays (0.529) and Indians (0.518). This paralleled the ethnic differences in lung volumes. The equations with both AS and SitHt as predictors provide the most accurate estimate of StndHt. Ethnic differences in upper body segment length may explain in part the lung volume differences.

Adult↗
PubMed2001

Cytochrome P4501A2 (CYP1A2) activity and lung cancer risk: a preliminary study among Chinese women in Singapore.

There is increasing evidence for the role of heterocyclic and other arylamines in carcinogenesis, including lung carcinogenesis. Chinese women have a high rate of lung cancer despite a low smoking prevalence, and studies in this population may provide useful information on risk factors other than smoking. Hepatic CYP1A2 and NAT2 are involved in the metabolism of carcinogenic arylamines, and NAT2 also catalyzes the detoxification pathway for these compounds. In this study, we examined the effect of CYP1A2 activity using a urinary caffeine metabolic ratio assay for 54 Chinese women with newly diagnosed lung cancer (including 28 adenocarcinomas) and 174 hospital controls. Among them, NAT2 genotype was available for 47 cases and 98 controls. There was no effect of CYP1A2 activity on overall risk of lung cancer in the study population [odds ratio (OR) 0.8, 95% confidence interval (CI) 0.4-1.6, adjusted for age at diagnosis, smoking and cruciferous vegetable intake]. For adenocarcinomas, the OR was 1.5, 95% CI 0.6-3.4. After further adjustment for NAT2 acetylator genotype, the OR for adenocarcinoma was 1.8 (95% CI 0.7-4.8). When the combined NAT2/CYP1A2 status was examined, women with slow NAT2 and rapid CYP1A2 activity were at highest risk (adjusted OR 6.9, 95% CI 1.3-37.6) relative to women with rapid NAT2 and slow CYP1A2 activity, for lung adenocarcinoma. While larger studies are needed to confirm or refute these results, they are consistent with a role for heterocyclic arylamines in lung carcinogenesis in this primarily non-smoking population.

Adenocarcinoma↗
PubMed2001

Force patterns of heel strike and toe off on different heel heights in normal walking.

This study investigated the changes of force patterns of the heel strike and toe off phases at different heel heights during normal walking. Ten healthy female college students wore running shoes, flat leather shoes and high heeled shoes while walking on a Kistler force platform at their self-comfortable paces. It was found that the high heeled shoes and the leather shoes generated significantly greater vertical impact forces and anterior-posterior forces in the toe off phase than those in the heel strike phase. Accumulated impulses did not show significant increase while the heel heights increased and total support time while wearing the high heeled shoes was significantly longer than while wearing the running shoes.

Adult↗
PubMed2001

A new asthma severity index: a predictor of near-fatal asthma?

Bronchial hyperresponsiveness (BHR), measured as the provocative dose of inhaled histamine or methacholine required to produce a 20% fall in forced expiratory volume in one second (FEV1) (PD20), is widely used as one of the indices of asthma severity. Excessive bronchoconstriction, reflected by the maximal percentage fall in forced vital capacity (FVC) at PD20 (deltaFVC %) during BHR testing, is considered to be the most important pathophysiological determinant in fatal asthma. The present study hypothesized that an index which combines both the ease of airway narrowing and excessive bronchoconstriction, deltaFVC %/log(PD20), may be better in assessing asthma severity, especially in those at risk of near-fatal attacks. The dose-response curves of 46 asthmatics who underwent methacholine challenge testing were studied. Group 1 (n=14) patients had mild disease, Group 2 (n=21) had moderate disease and Group 3 (n=11) had severe disease, as classified according to the Global Initiative for Asthma. Nine patients had prior intubation for near-fatal asthma. deltaFVC %/log (PD20) was better than deltaFVC % and PD20 in categorizing patients into the three severity groups (p<0.0001), but more importantly, it was able to discriminate patients with previous intubation from those without (p=0.04). It also correlated better with FEV1 (% predicted), frequency of symptoms and inhaled steroid requirement than either index alone. It is concluded that the percentage fall in forced vital capacity/log of the provocative dose causing a 20% fall in forced expiratory volume in one second combines information on the ease and excessive degrees of airway narrowing in asthma. This new index may be better at assessing asthma severity and in discriminating those at risk of near-fatal attacks.

Adult↗
PubMed2001

Diffuse panbronchiolitis--a case report.

Diffuse panbronchiolitis (DPB) is a chronic progressive obstructive disease of the airways. Of unknown aetiology, it is responsive to macrolide therapy. Although not uncommon among the Japanese, it is rare in other parts of the world. We report a case of DPB in a Chinese patient in Singapore.

Anti-Bacterial Agents↗
PubMed2001

Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and lung cancer risk among Chinese women in Singapore.

Chinese populations consume a diet relatively high in isothiocyanates (ITCs), a derivative of cruciferous vegetables known to have cancer-protective effects. This class of compounds is metabolized by the glutathione S-transferase family of enzymes, which are also involved in the detoxification of tobacco-related carcinogens such as polycyclic aromatic hydrocarbons and alkyl halides. We evaluated the association between dietary isothiocyanate intake, GSTM1 and GSTT1 polymorphisms, and lung cancer risk in 420 Chinese women: 233 histologically confirmed lung cancer patients and 187 hospital controls. Among these, 58.8% of cases and 90.3% of controls were lifetime nonsmokers. An allele-specific PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in DNA isolated from peripheral blood. Higher weekly intake of ITCs (above the control median value of 53.0 micromol) reduced the risk of lung cancer to a greater extent in smokers [adjusted odds ratio (OR), 0.31; 95% confidence interval (CI), 0.10-0.98] than nonsmokers (OR, 0.70; 95% CI, 0.45-1.11). The inverse association was stronger among subjects with homozygous deletion of GSTM1 and/or GSTT1. Among nonsmokers with GSTM1-null genotype, higher intake of ITCs significantly reduced the risk of lung cancer (OR, 0.54; 95% CI, 0.30-0.95), an effect not seen among those with detectable GSTM1 (OR, 1.07; 95% CI, 0.50-2.29). Our results, in a Chinese female population, are consistent with the hypothesis that ITC is inversely related to the risk of lung cancer, and we show that among nonsmokers this effect may be primarily confined to GST-null individuals. Conjugation and elimination of ITCs is enhanced in GST-non-null relative to -null individuals, such that the GST metabolic genotype modifies the protective effect of ITCs on lung cancer development.

Adult↗
PubMed2001

Deep vein thrombosis in patients admitted for exacerbation of chronic obstructive pulmonary disease.

INTRODUCTION: There is a lack of data on the prevalence of deep vein thrombosis and pulmonary embolism in patients admitted to hospital for exacerbation of chronic obstructive pulmonary disease. Studies have found that most pulmonary embolism originate from deep vein thrombosis in the lower limbs, thus the prevalence of deep vein thrombosis may give an accurate reflection of the prevalence of pulmonary embolism. The aim of our study was to determine the prevalence of deep vein thrombosis in these patients, using duplex ultrasound of the lower limbs as the screening tool. METHODS: Thirty-three male patients admitted to the general ward for exacerbation of chronic obstructive pulmonary disease were screened for presence of deep vein thrombosis of the lower limbs using duplex ultrasound scan. RESULT: No patient in this study was found to have deep vein thrombosis of the lower limbs. CONCLUSIONS: The prevalence of deep vein thrombosis in local patients admitted for exacerbation of chronic obstructive pulmonary disease is likely to be low. We do not recommend the use of duplex ultrasound to screen for deep vein thrombosis in this group of patients.

Aged↗
PubMed2001

Impact of an asthma carepath on the management of acute asthma exacerbations.

INTRODUCTION: Clinical pathways are being developed to standardise the management of acute asthma with the aim of improving asthma care. We evaluated the impact of an asthma carepath (CP), developed and instituted at a large community-based teaching hospital. MATERIALS AND METHODS: Case records of consecutive asthma cases were reviewed after the implementation of a new asthma CP (November 1999 to March 2000). Data from July to October 1998 were used as historical control data [pre-carepath (pre-CP)]. Data collected included patient demographics, investigations performed, treatment prescribed, use of peak expiratory flow rate (PEFR) monitoring, length of stay (LOS) and asthma relapse rates. RESULTS: One hundred and eighteen consecutive cases treated according to CP were compared with 67 pre-CP controls. There was no significant difference between the two groups with regard to LOS, use of PEFR monitoring, use of systemic steroids in hospital or asthma relapse after discharge (P > 0.05). A significant decrease in sputum tests (34.3% pre-CP versus 18.6% CP, P = 0.017) and use of antibiotics (62.7% pre-CP versus 30.4% CP, P < 0.001) was observed for patients on CP. The proportion of patients who had their salbutamol reviewed (49.3% pre-CP versus 73.7% CP, P = 0.001) and oxygen reviewed (25.8% pre-CP versus 73.8% CP, P = 0.004) was also significantly higher for cases on CP. CONCLUSION: Although the asthma CP did not significantly reduce LOS or early relapse, it was associated with a significant reduction of the use of sputum tests and antibiotics. Review of salbutamol and oxygen as treatment was also more likely.

Adult↗
PubMed2001

Occupational asthma in Singapore.

AIM: Since the first notified case of occupational asthma in 1983, a total of 90 cases were confirmed as on 31st December 1999. In this study, demographic data, causative agents and impact on the workers were described. METHODS: The data was derived from notifications to the Ministry of Manpower and referrals to the Occupational Lung Disease Clinic jointly run with Department of Respiratory Medicine, Tan Tock Seng Hospital. RESULTS: Of the 90 cases, 19 (21%) were females and 71 (79%) were males. There were 48 (53%) Chinese, 22 (24%) Malays, 14 (16%) Indians and 6 (7%) of other ethnic origins. The mean age at diagnosis was 35.8 +/- 9.3 yrs. The mean duration of exposure prior to onset of symptoms was 34.9 +/- 57.3 months. The most common causative agent was isocyanates (28 cases, 31%) followed by solder flux (12 cases, 13%) and welding fumes (8 cases, 9%) respectively. Thirteen (14.4%) workers were assessed to have permanent disability under the Workmen's Compensation Act. CONCLUSIONS: Since 1990, occupational asthma has overtaken silicosis and asbestosis as the most common occupational lung disease in Singapore. The most common causative agent is isocyanates. Occupational asthma is a condition associated with disability in the workplace and may still be largely under-reported.

Adult↗
PubMed2000

Direct protein-protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors.

GABA(A) (gamma-aminobutyric-acid A) and dopamine D1 and D5 receptors represent two structurally and functionally divergent families of neurotransmitter receptors. The former comprises a class of multi-subunit ligand-gated channels mediating fast interneuronal synaptic transmission, whereas the latter belongs to the seven-transmembrane-domain single-polypeptide receptor superfamily that exerts its biological effects, including the modulation of GABA(A) receptor function, through the activation of second-messenger signalling cascades by G proteins. Here we show that GABA(A)-ligand-gated channels complex selectively with D5 receptors through the direct binding of the D5 carboxy-terminal domain with the second intracellular loop of the GABA(A) gamma2(short) receptor subunit. This physical association enables mutually inhibitory functional interactions between these receptor systems. The data highlight a previously unknown signal transduction mechanism whereby subtype-selective G-protein-coupled receptors dynamically regulate synaptic strength independently of classically defined second-messenger systems, and provide a heuristic framework in which to view these receptor systems in the maintenance of psychomotor disease states.

Amino Acid Motifs↗
PubMed2000

Endogenous Zn(2+) is required for the induction of long-term potentiation at rat hippocampal mossy fiber-CA3 synapses.

The functional role of the abundant Zn(2+) found in some hippocampal synapses has been an enigma. We show here, using N-[6-methoxy-8-quinolyl]-P-toluenesulfonamide (TSQ) staining, that chelatable-Zn(2+) can be removed from hippocampal synaptic boutons using dietary depletion or with Zn(2+) chelators. A chronic dietary deficiency of bouton Zn(2+) resulted in the impairment of long-term potentiation (LTP) at mossy fiber-CA3 synapses. The averaged normalized fEPSP slope 30 min after tetanus was 209 +/- 28% of baseline value in control (mean +/- SEM, n = 10), and 118 +/- 12% in Zn(2+)-deficient rats (mean +/- SEM, n = 12, P < 0.01). In the deficient rats with Zn(2+) supplements, mossy fiber LTP returned to normal levels. The acute depletion of bouton Zn(2+) in the hippocampal slice with membrane-permeable Zn(2+) chelators, dithizone, or diethyldithiocarbamic acid (DEDTC) blocked the induction of mossy fiber LTP. The mean amplitudes of EPSCs after tetanus were 194 +/- 22% of baseline value in control (n = 5), compared to 108 +/- 14% in dithizone (n = 6) and 101 +/- 12% in DEDTC (n = 5). The averaged value of LTP, at the associational commisural fiber-CA3 synapses, was 193 +/- 20% in the control (n = 6), compared to 182 +/- 21% (n = 6, P > 0.1) in the presence of dithizone. The blockade of mossy fiber LTP by dithizone was reversible after washout. In addition, normal LTP could be induced by tetanus if exogenous Zn(2+) was applied immediately following dithizone. Our results indicate that the endogenous Zn(2+) is specifically required for LTP induction at the mossy fiber input into CA3 neurons.

Animals↗