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Biomedical subjects

S Wee

Publications and source records attributed to S Wee.

At least 19 recordsLinked to original sources
PubMed2005

Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs.

It has been reported that among drugs with mixed actions on central nervous system monoamine systems, increased serotonergic activity is associated with decreased potency as a reinforcer. The present experiment was designed to examine this relationship for amphetamine analogs that varied in serotonin releasing potency and to evaluate whether serotonergic actions can affect reinforcing efficacy. Compounds PAL 313 and 314 are para- and meta-methylamphetamine, respectively. PAL 303 and 353 are para- and meta-fluoroamphetamine, respectively. All compounds had similar potencies as in vitro releasers of dopamine (DA) and norepinephrine (NE) but differed in potency for 5-hydroxytryptamine (serotonin) (5-HT) release [EC(50) (nanomolar) PAL 313 = 53.4; PAL 314 = 218; PAL 303 = 939; PAL 353 = 1937]. When made available to rhesus monkeys (Macaca mulatta)(n = 4) for self-administration under a fixed-ratio 25 schedule, all were positive reinforcers with biphasic dose-response functions (0.003-1.0 mg/kg) and were equipotent. PAL 313 was self-administered at a lower rate than the other compounds, which were indistinguishable. Under a progressive-ratio schedule (n = 5), all drugs were positive reinforcers. Dose-response functions increased to a maximum or were biphasic (0.01-1.0 mg/kg), and drugs were equipotent. At maximum, PAL 313 maintained less responding than other PAL drugs, which maintained similar maxima. Thus, all compounds were positive reinforcers under both schedules, consistent with their potent DA actions. Responding was lower when 5-HT potency was higher and comparable with DA and NE potency. The results suggest that the mechanism for this effect involves a decrease in reinforcing potency and efficacy among monoamine releasing agents when 5-HT releasing potency is increased relative to DA.

Amphetamine↗
PubMed2004

Determinants of inconsistent condom use with female sex workers among men attending the STD clinic in Singapore.

BACKGROUND/OBJECTIVES: Female sex workers and their male clients have been identified as risk groups for the transmission of STDs and HIV. Behavioural interventions targeting clients need to address inconsistent condom use among them. The aim of the study is to assess the sociodemographic, behavioural, and psychological factors associated with inconsistent condom use among clients of sex workers. METHODS: 229 male patients attending the STD clinic in Singapore who reported paying for sex in the previous 6 months were interviewed. Response rate was 91%. RESULTS: Overall, 45% used condoms inconsistently; these clients were more likely to have poor STD knowledge, visit sex workers five or more times in the past 6 months, have lower self efficacy, less favourable social norms for condom use, and more likely to forget condom use when intoxicated (alcohol impaired decision making). CONCLUSIONS: Behavioural interventions for clients need to improve STD/HIV transmission knowledge and focus on improving client's self efficacy in using condoms.

Adolescent↗
PubMed2000

Factors associated with condom use for oral sex among female brothel-based sex workers in Singapore.

BACKGROUND AND OBJECTIVE: The prevalence of oral sex increased from 27.1% in 1992 to 81.1% in 1997, with a concomitant increase in pharyngeal gonorrhea, among female sex workers in Singapore. The extent of condom use for oral sex among them is unknown. GOAL: To determine the prevalence of and factors associated with consistent condom use during oral sex. STUDY DESIGN: A cross-sectional study of 225 women randomly selected from the surveillance scheme register of female brothel-based sex workers with a history of oral sex documented in their medical records. RESULTS: Slightly more than half (56.9%) consistently used condoms for oral sex compared to 97% for vaginal sex. Condom use was significantly higher among middle than high class sex workers (adjusted rate ratio: 1.52, 95% CI: 1.01-2.29) and those with negotiation skills (adjusted rate ratio: 1.95, 95% CI: 1.32-2.07). CONCLUSION: Sex workers should be taught skills to negotiate condom use for oral sex.

Adult↗
PubMed2000

A prospective study on condom slippage and breakage among female brothel-based sex workers in Singapore.

BACKGROUND: Concerns about the effectiveness of condoms in preventing sexually transmitted diseases have been raised. Data are lacking on condom failure and its associated factors among sex workers in Southeast Asia. GOAL: To assess factors associated with condom breakage and slippage. STUDY DESIGN: A prospective study on condom breakage and slippage over a 1-day period was conducted among 219 female brothel-based sex workers in Singapore in 1997. RESULTS: Condom breakage and slippage rates among 1,885 episodes of condom use were 1.2% (95% CI, 0.7-1.8) and 2.1% (95% CI, 1.2-3.0), respectively. After adjusting for intracluster effects and confounders, condom breakage and slippage were significantly associated with duration of sex work and spontaneity of clients to use condoms. CONCLUSION: Condom use among sex workers should be promoted in view of the low failure rates. Strategies to reduce condom breakage and slippage should be directed at sex workers with increased risk of condom failure.

Adult↗
PubMed2000

Sex workers' perspectives on condom use for oral sex with clients: a qualitative study.

The authors conducted in-depth interviews with 46 female brothel-based sex workers to explore their perceived barriers and approaches in getting clients to use condoms for oral sex. Reasons given by sex workers for not using condoms for oral sex as compared to vaginal sex included self-perception of low vulnerability to AIDS and sexually transmitted infections, misconceptions on transmission of the HIV virus, lack of negotiation skills, lack of support from brothel keepers and peers, and unpleasant taste and smell of condoms. Some sex workers could get all their clients to use condoms for oral sex by using negotiation skills, including the positive approach, the fear approach, the emotional appeal approach, and the assertive approach. Findings from this study would help design more appropriate messages and improve negotiation skills of sex workers to increase consistent condom use for oral sex.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Isolation and identification of Fur binding genes in Escherichia coli.

Fur (ferric uptake regulation) binding fragments were isolated by in vitro binding of purified Fur protein with Sau3AI-digested genomic DNA fragments. The Fur-bound DNA fragments were filtered on nitrocellulose paper, isolated, cloned, and sequenced. The protein binding was confirmed by gel retardation assay for five DNA fragments. The sequence data were used to identify the genes by comparison with the GenBank data. The proposed Fur binding regions lie on or near the putative promoter regions of marAB (multiple antibiotic resistance), pyrC (dihydroorotase), mreB (mecillinam resistance) and an unidentified gene (ecouw93) near argI and in the middle of the treBC (trehalose permease enzyme II) coding region. The proposed Fur binding sites of the known iron regulating operators including the genes of this work are AAT(pyrimidine) and A(purine)TT. The two conserved sequences are 10 bases apart and palindromic to each other, which might suggest the classical pattern of protein binding toward one side of the DNA in contrast to the concept of the Fur protein wrapping around the DNA.

Bacterial Proteins↗
PubMed1999

In vivo generation of C4d, Bb, iC3b, and SC5b-9 after OKT3 administration in kidney and lung transplant recipients.

BACKGROUND: OKT3 monoclonal antibody therapy results in an acute clinical syndrome (ACS) associated with the release of tumor necrosis factor and sequestration of neutrophils in the lungs. We have previously shown that inhibition of tumor necrosis factor does not completely eliminate OKT3-ACS, suggesting that other factors also contribute to the ACS. The current studies analyzed complement activation in vivo during the first hour after OKT3 administration. METHODS: Renal (n=4) and lung (n=4) transplant recipients received OKT3 as treatment for rejection and induction therapy, respectively. Complement activation products C4d, Bb, iC3b, and SC5b-9 were measured by ELISA. Hemodynamic parameters were also monitored in the lung transplant recipients. Neutrophil expression of CD11a, CD11b, and CD18 was monitored by flow cytometry. Controls included patients receiving methylprednisolone for rejection (n=4), two adults with adult respiratory distress syndrome who received extracorporeal membrane oxygenation, and normal volunteers (n=5). P values less than 0.05 (*) were considered significant. RESULTS: Increases in the plasma levels of C4d, Bb, iC3b, and SC5b-9 were observed in seven of eight patients after OKT3 administration. Mean values (n=8) at 0, 15, and 60 min (in microg/ml) were as follows-C4d: 1.865, 2.644*, and 2.607*; Bb: 0.245, 0.411, and 0.385; iC3b: 10.881, 17.242*, and 15.145*; and SC5b-9: 0.232, 0.269, and 0.302*. An increase in CD11b and CD18 and a decrease of CD11a on neutrophils in parallel with complement activation was observed. In lung transplant recipients, C3 activation correlated with increases in mean pulmonary and central venous pressures (P<0.05). As compared with extracorporeal membrane oxygenation, which activated classical and alternative pathways, OKT3 predominantly activated complement by the classical pathway. Methylprednisolone pulses did not activate complement. CONCLUSIONS: Complement activation is an early event after OKT3 administration and is associated with the increased expression of adhesion molecules on neutrophils and with pulmonary hemodynamic changes. Effective therapeutic approaches to the control of early monoclonal antibody side effects may require measures that limit complement activation in addition to reducing cytokine activity.

Adult↗
PubMed1999

Sexually transmitted diseases and condom use among female freelance and brothel-based sex workers in Singapore.

BACKGROUND AND OBJECTIVES: Most studies in Asia exclude freelance female sex workers because of difficulties in access and the illegality of their work. Data are lacking on their risk behaviors. GOAL: To compare sexually transmitted disease (STD) rates, condom use, and health screening behavior between freelance and brothel-based sex workers in Singapore. STUDY DESIGN: This is a cross-sectional survey of 111 free-lance sex workers arrested from November 1996 to March 1997 for illicit prostitution and 333 randomly selected brothel-based sex workers. All were tested for STDs. RESULTS: STDs were significantly more prevalent among freelance than brothel-based sex workers (34.8% vs. 24.0%). Inconsistent condom use was significantly higher among freelance than brothel-based sex workers and was significantly associated with younger age, decreasing number of clients, and perception of non-condom use among peers. CONCLUSION: Educational programs to promote condom use should target freelance sex workers and their clients.

Adult↗
PubMed1999

Sociodemographic and lifestyle factors associated with constipation in an elderly Asian community.

OBJECTIVE: We surveyed elderly individuals in an Asian community to determine the prevalence of constipation and its association with sociodemographic and lifestyle factors. This information will be used to plan a health promotion program for the elderly. METHODS: A random sample of 2807 residents aged > or = 60 yr in Singapore were interviewed in their homes, using a standardized questionnaire. The response rate was 87.4% (n = 2454). RESULTS: The overall age- and gender-adjusted prevalence rate of functional constipation was 11.6 per 100 persons (95% confidence interval [CI], 11.4-11.7). There were no gender or ethnic differences in constipation rates. Increased rates of constipation were significantly associated with advancing age. We found a significant dose-response relationship of increased constipation rates with decreased intake of rice, increased intake of Chinese tea, and number of chronic illnesses and medications, after controlling for potential confounders. Constipation was also significantly associated with lower intake of fruits and vegetables, but no dose-response gradient was seen. CONCLUSIONS: Patients taking many medications should be monitored for constipation and given advice to avoid constipating factors. Further studies are needed to establish the causal-effect relationship of rice and Chinese tea with constipation.

Aged↗
PubMed1999

Correlates of leisure-time physical activity in an elderly population in Singapore.

OBJECTIVES: This study assessed correlates of leisure-time physical activity among the elderly in Singapore. METHODS: A cross-sectional household survey was conducted in 1998 with 2494 subjects 60 years and older. RESULTS: Regular leisure-time physical activity was practiced by 47.0% of men and 38.5% of women. It was significantly correlated with family support, proportion of family members exercising, awareness of benefits of exercise, and healthy dietary habits. Other significant but negative correlates were smoking and barriers to exercise, such as lack of time and poor health. CONCLUSIONS: Exercise programs for the elderly should aim at helping them overcome barriers to exercise, informing them of the benefits of exercise, and involving their families.

Aged↗
PubMed1998

Structure-function analysis of FLT3 ligand-FLT3 receptor interactions using a rapid functional screen.

FLT3 ligand (FLT3L) stimulates primitive hematopoietic cells by binding to and activating the FLT3 receptor (FLT3R). We carried out a structure-activity study of human FLT3L in order to define the residues involved in receptor binding. We developed a rapid method to screen randomly mutagenized FLT3L using a FLT3R-Fc fusion protein to probe the relative binding activities of mutated ligand. Approximately 60,000 potential mutants were screened, and the DNA from 59 clones was sequenced. Thirty-one single amino acid substitutions at 24 positions of FLT3L either enhanced or reduced activity in receptor binding and cell proliferation assays. Eleven representative proteins were purified and analyzed for receptor affinity, specific activity, and physical properties. Receptor affinity and bioactivity were highly correlated. FLT3L affinity for receptor improved when four individual mutations that enhance FLT3L receptor affinity were combined in a single molecule. A model of FLT3L three-dimensional structure was generated based on sequence alignment and x-ray structure of macrophage colony-stimulating factor. Most residues implicated in receptor binding are widely dispersed in the primary structure of FLT3L, yet they localize to a surface patch in the tertiary model. A mutation that maps to and is predicted to disrupt the proposed dimerization interface between FLT3L monomers exhibits a Stokes radius that is concentration-dependent, suggesting that this mutation disrupts the FLT3L dimer.

Amino Acid Sequence↗
PubMed1998

Protein release from alginate matrices.

There are a variety of both natural and synthetic polymeric systems that have been investigated for the controlled release of proteins. Many of the procedures employed to incorporate proteins into a polymeric matrix can be harsh and often cause denaturation of the active agent. Alginate, a naturally occurring biopolymer extracted from brown algae (kelp), has several unique properties that have enabled it to be used as a matrix for the entrapment and/or delivery of a variety of biological agents. Alginate polymers are a family of linear unbranched polysaccharides which contain varying amounts of 1,4'-linked beta-D-mannuronic acid and alpha-L-guluronic acid residues. The residues may vary widely in composition and sequence and are arranged in a pattern of blocks along the chain. Alginate can be ionically crosslinked by the addition of divalent cations in aqueous solution. The relatively mild gelation process has enabled not only proteins, but cells and DNA to be incorporated into alginate matrices with retention of full biological activity. Furthermore, by selection of the type of alginate and coating agent, the pore size, degradation rate, and ultimately release kinetics can be controlled. Gels of different morphologies can be prepared including large block matrices, large beads (>1 mm in diameter) and microbeads (<0.2 mm in diameter). In situ gelling systems have also been made by the application of alginate to the cornea, or on the surfaces of wounds. Alginate is a bioadhesive polymer which can be advantageous for the site specific delivery to mucosal tissues. All of these properties, in addition to the nonimmunogenicity of alginate, have led to an increased use of this polymer as a protein delivery system. This review will discuss the chemistry of alginate, its gelation mechanisms, and the physical properties of alginate gels. Emphasis will be placed on applications in which biomolecules have been incorporated into and released from alginate systems.

Journal Article↗
PubMed1997

Biological effects and fate of a soluble, dimeric, 80-kDa tumor necrosis factor receptor in renal transplant recipients who receive OKT3 therapy.

A preliminary clinical study of renal allograft recipients revealed that a dimeric form of the human 80 kDa soluble receptor (sTNFR:Fc) for tumor necrosis factor (TNF) is well tolerated and attenuates the OKT3-induced acute clinical syndrome. The current study determined the in vivo biological effects and fate of sTNFR:Fc in these patients. Serial assessment of both antigenic and biological activities of circulating TNF and sTNFR:Fc have led to the following observations. (1) Although control patients typically responded to the first OKT3 injection with a rapid increase of biologically active TNFalpha, patients on sTNFR:Fc therapy had markedly higher serum TNFalpha antigenic levels, but no detectable bioactivity. Thus, sTNFR:Fc functioned as a potent antagonist, despite its cytokine-carrier effect. (2) Peak sTNFR:Fc levels averaging 800 and 2500 ng/ml were routinely achieved in vivo, using the low-dose (0.05 mg/kg) and high-dose (0.15 mg/kg) protocols. (3) The half-life of circulating sTNFR:Fc was estimated to be approximately 4.4 days, and levels of p80 receptors in treated patients remained significantly above those in control patients for at least 20 days. (4) In vitro blocking studies demonstrated that circulating sTNFR:Fc remained biologically active for 2 weeks. These results demonstrate that under current protocols, significant serum levels of sTNFR:Fc, capable of effectively neutralizing TNF activity over prolonged periods, can be achieved. The persistent OKT3 side effects observed, despite sTNFR:Fc therapy, are therefore likely to be caused by factors other than TNF.

Dimerization↗
PubMed1996

Evaluation of recombinant human soluble dimeric tumor necrosis factor receptor for prevention of OKT3-associated acute clinical syndrome.

Tumor necrosis factor alpha (TNFa) has been shown to be the primary cytokine responsible for the OKT3-induced acute clinical syndrome (OKT3-ACS). Recombinant human soluble tumor necrosis factor receptor (TNFR:Fc) is a dimer of the p80 TNF receptor, which binds both TNFa and lymphotoxin (LT). Renal allograft recipients undergoing OKT3 therapy for steroid-resistant rejection were randomized to receive OKT3 alone or in combination with TNFR:Fc to determine its safety and efficacy in decreasing the severity of OKT3-ACS and in restoring renal function. Six of 12 patients were given TNFR:Fc prior to each of the first two injections of OKT3. All patients were monitored for manifestations of OKT3-ACS and changes in renal function. In addition, serial serum samples were assayed for TNFa and TNFR:Fc levels (ELISA) and TNFa bioactivity (L929). No adverse side effects were identified in patients receiving TNFR:Fc. Patients treated with TNFR:Fc had significantly fewer symptoms by day 2 of OKT3, and had a lower overall incidence of chills and arthralgias. Renal dysfunction reversed within 24 hr in the TNFR:Fc-treated group in contrast to the 48-72-hr delay in the control group. Antigenic TNFa levels increased in the control group from < 10 pg/ml pre OKT3 to a mean peak level of 30 +/- 13 pg/ml on day 1 and decreased to pretreatment levels by day 2. TNFR:Fc-treated patients had a mean peak TNFa level of 235 +/- 135 pg/ml, suggesting a carrier effect of TNFR:Fc. In contrast, bioactivity was barely detectable (mean 20 +/- 14 pg/ml) in the day 1 samples from TNFR:Fc-treated patients, whereas significant bioactivity (peak mean 60 +/- 35 pg/ml) was detected in sera from control patients. TNF receptor levels reached 600 ng/ml in treated patients and remained elevated for up to 18 days confirming the long half-life of TNFR:Fc. This phase 1 trial demonstrates that TNFR:Fc is well tolerated and may limit the severity of OKT3-ACS. The most significant observation was a more rapid improvement in renal function in the TNFR:Fc-treated patients. The absence of TNFa bioactivity indicates that TNFR:Fc functions as a TNF antagonist. Further evaluation of higher doses of TNFR:Fc in OKT3-treated patients is currently in progress.

Acute Disease↗
PubMed1996

Purification and characterization of a 28 kDa cytosolic inhibitor of cholesteryl ester hydrolases in rat testis.

A 28 kDa inhibitory protein was purified from rat testis cytosol by sequential 40-65% ammonium sulfate precipitation, cation exchange chromatography, anion exchange chromatography, and preparative SDS-polyacrylamide gel electrophoresis. The heat-stable, trypsin-labile protein exhibited nonenzymatic, concentration-dependent inhibition of testicular and pancreatic cholesteryl ester hydrolases at all stages of purification. Copurifying at each stage was a 26.5 kDa protein which comprised 25% of the mass of the two proteins. Polyclonal antibodies raised to either or both 28 kDa and 26.5 kDa proteins by direct injection of excised electrophoretic bands cross-reacted with both proteins on western blots, immunoprecipitated both proteins, and neutralized inhibitory activity. Amino acid compositions of the individual proteins electroeluted from SDS-polyacrylamide gels were different from those of other surface-active proteins of similar molecular weights. Both proteins exhibited identical pl of 4.8 on chromatofocusing columns and two-dimensional gel electrophoresis. Although the subcellular distribution of the 28 kDa protein is unknown, its testicular cytosolic concentration, calculated from the purified protein mass, was 8 X 10(-9) mols/L, which probably underestimates the actual concentration by an order of magnitude. This is greater than the minimum concentration required for in vitro inhibition (10(-9) mols/L), consistent with a physiological role for this protein.

Amino Acids↗
PubMed1995

Inhibition of the effects of TNF in renal allograft recipients using recombinant human dimeric tumor necrosis factor receptors.

Tumor necrosis factor alpha (TNFa) and lymphotoxin (LT) or TNF beta are closely linked cytokines produced by macrophages and activated T lymphocytes, which play important regulatory roles in the immune response to allografts. They have also been implicated as mediators of the adverse reactions observed during OKT3 therapy. Therefore, anti-TNF agents could be useful both for immunosuppression and for limiting the systemic response observed in patients receiving OKT3. Recombinant TNFR:Fc is a fusion protein that binds TNFa and LT, thereby neutralizing their effects in vitro. The present study investigates the potential clinical application of TNFR:Fc in a nonhuman primate renal allograft model. Cynomolgus renal allograft recipients were treated with TNFR:Fc induction therapy alone or in combination with subtherapeutic doses of cyclosporine. Control animals received no immunosuppression or subtherapeutic cyclosporine. TNFR:Fc, administered as the only immunosuppressive agent, successfully prolonged renal allograft survival in the majority of treated animals. The prolongation of allograft survival was even more impressive when TNFR:Fc was combined with subtherapeutic doses of cyclosporine. Onset of rejection was significantly delayed as well in the TNFR:Fc treated groups. No adverse side effects were observed in any of the TNFR:Fc treated animals. Precursor cytotoxic T cells were detected in peripheral blood samples of treated recipients but the level of effector CTLs in vivo was below the threshold of detection. These results demonstrate that TNFR:Fc can be safely administered and is effective in prolonging renal allograft survival and in delaying the onset of rejection when administered alone or in combination with cyclosporine.

Animals↗