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Biomedical subjects

S C Ng

Publications and source records attributed to S C Ng.

At least 37 records · Page 2Linked to original sources

Spin-wave quantization in ferromagnetic nickel nanowires.

The dynamical properties of uniform two-dimensional arrays of nickel nanowires have been investigated by inelastic light scattering. Multiple spin waves are observed that are in accordance with dipole-exchange theory predictions for the quantization of bulk spin waves. This first study of the spin-wave dynamics in ferromagnetic nanowire arrays reveals strong mode quantization effects and indications of a subtle magnetic interplay between nanowires. The results show that it is important to take proper account of these effects for the fundamental physics and future technological developments of magnetic nanowires.

Journal Article↗

Osteoporosis in relation to menopause.

With an ageing population in Singapore, it is anticipated that postmenopausal osteoporosis and related fractures will be an increasingly important health issue in the coming decades. Oestrogen replacement therapy has a long history of use to treat postmenopausal problems including osteoporosis. The availability of other potent agents such as bisphosphonates, calcitonin and selective oestrogen receptor modulators has enriched the therapeutic options. This article reviews the evidence for the choice of appropriate agents, and strategies to prevent and treat postmenopausal osteoporosis.

Age Distribution↗

Hormone replacement therapy (HRT) and ischaemic heart disease: getting to the heart of the matter.

Numerous observational studies have previously shown that estrogen therapy (ERT) or estrogen/progestin hormone replacement therapy (HRT) can significantly reduce the risk of Coronary Artery Disease (CAD) in healthy postmenopausal women by up to 50%. However, due to statistical limitations inherent in these earlier studies, several large randomised trials are now under way. The results from some of these randomised trials are expected sometime in 2005 and will certainly help confirm or refute the present perceived cardio-protective effects of ERT/HRT in healthy menopausal women. On the other hand, the role of hormonal therapy in menopausal women with established CAD is more controversial. Although results from earlier observational trials have been encouraging, more recent randomised controlled data from the Heart and Estrogen/Progestin Replacement (HER) study and the Estrogen Replacement and Atherosclerosis (ERA) study have been more sober. In fact, both have generally reported on the failure of ERT/HRT to reduce the overall rate of ischaemic cardiovascular events or to halt the progression of coronary atherosclerosis in menopausal women with established CAD. However, these studies are not without their own limitations. As such, more future trials will be needed before the role of postmenopausal hormone therapy in the secondary prevention of CAD can be firmly established.

Coronary Disease↗

The impact of minimal access surgery on gynaecological surgery in a university gynaecological unit over a 10-year period from 1991 to 2000.

OBJECTIVE: To assess the impact of minimal access surgery in replacing traditional open approach of surgery for benign gynaecological pathology. SETTING: Gynaecological unit in a university hospital. METHODOLOGY: All surgical procedures for the treatment of ectopic pregnancy, benign ovarian cyst, myomectomy, and hysterectomy for benign gynaecological pathology over a 10-year period (1991 to 2000) were studied. The percentages of procedures performed with the minimal access approach were compared with the traditional open approach over the study period. FINDINGS: The percentage of ectopic pregnancies treated laparoscopically has increased from a low of 27% in the initial two-year period of 1991-92 to stabilise at approximately 70% at the end of the decade. Laparoscopic approach for the treatment of benign ovarian cysts constituted just 31% of cases in the initial period (1991-92) and rose steadily to stabilise at approximately 50% of cases during the last four years of the decade. The proportion of advanced minimal access procedures such as myomectomy and hysterectomy increased at a more gradual pace during the decade. By 1999-2000, laparoscopic and hysteroscopic myomectomy constituted about 30% of all myomectomies but laparoscopic hysterectomy accounted for just about 5% of all hysterectomies performed. CONCLUSIONS: Minimal access surgery has largely replaced the open approach for the treatment of ectopic pregnancy and benign ovarian cysts. Advanced minimal access procedures such as myomectomy and hysterectomy showed a rising trend through the decade, but still accounted for a minority of procedures at the end of the decade.

Female↗

Somatic cell nuclear transfer (cloning): implications for the medical practitioner.

The current century will bring tremendous changes to the science and the practice of medicine. This century will be acknowledged as the century of Biology as the fusion of molecular genetics and experimental embryology pushes the barriers of science beyond perimeters that we have thought existed, as much as the past century was the century of Physics, with all the exact scientific calculations and predictions, resulting in electricity, nuclear power and quantum physics. The first major breakthrough has been the pioneering work of Wilmut and Campbell, first with the birth of Megan and Moran in 1995 (1), followed by the birth of Dolly the sheep, the first reported mammalian clone from a fully differentiated adult cell, reported in July 1996 (2). However, current cloning techniques are an extension of over 40 years of research using nuclei derived from non-human embryonic and fetal cells. However, following the birth of Dolly, the prospects of cloning technology have extended to ethically hazier areas of human cloning and embryonic stem cell research. This review hopes to bring the reader closer to the science and the ethics of this new technology, and what the implications are for the medical practitioner.

Animals↗

A-204197, a new tubulin-binding agent with antimitotic activity in tumor cell lines resistant to known microtubule inhibitors.

Drug resistance is a prevalent problem in the treatment of neoplastic disease, and the effectiveness of many clinically useful drugs is limited by the fact that they are substrates for the efflux pump, P-glycoprotein. Because there is a need for new compounds that are effective in treating drug-resistant tumors, we tested A-204197 (4-[4-acetyl-4,5-dihydro-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl]-N,N-dimethylbenzeneamine), a novel oxadiazoline derivative with antiproliferative properties, on cell lines that were either sensitive or resistant to known microtubule inhibitors. Cell lines that were resistant to paclitaxel, vinblastine, or colchicine were equally sensitive to A-204197 (proliferation IC50s ranging from 36 to 48 nM) despite their expression levels of P-glycoprotein. The effect of A-204197 on cell growth was associated with cell cycle arrest in G2-M, increased phosphorylation of select G2-M checkpoint proteins, and apoptosis. In competition-binding assays, A-204197 competed with [3H]-labeled colchicine for binding to tubulin (K(i) = 0.75 microM); however, it did not compete with [3H]-labeled paclitaxel. A-204197 prevented tubulin polymerization in a dose-dependent manner (IC50 = 4.5 microM) in vitro and depolymerized microtubules in a time-dependent manner in cultured cells. These findings indicate A-204197 is a promising new tubulin-binding compound with antimitotic activity that has potential for treating neoplastic diseases with greater efficacy than currently used antimitotic agents.

Antineoplastic Agents↗

Novel sulfonate derivatives: potent antimitotic agents.

The synthesis and biological evaluation of novel sulfonate analogues of E-7010 are reported. Several of the compounds are potent inhibitors of cell proliferation and tubulin polymerization. Importantly, these compounds are also active against P-glycoprotein positive (+) cancer cells, which are resistant to many other antitumor agents.

Aminophenols↗

Novel sulfonate analogues of combretastatin A-4: potent antimitotic agents.

Sulfonate analogues of combretastatin A-4 have been prepared. These compounds compete with colchicine and combretastatin A-4 for the colchicine binding site on tubulin and are potent inhibitors of tubulin polymerization and cell proliferation. Importantly, these compounds also inhibit the proliferation of P-glycoprotein positive (+) cancer cells, which are resistant to many other antitumor agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Enhanced dehydroepiandrosterone synthesis by amnion compared to chorion: a comparative study using the reverse-isotope dilution technique.

With a view to establishing whether the term human fetal membranes possess the enzymic ability to synthesize dehydroepiandrosterone (DHEA) from pregnenolone, homogenates of amnion and chorion obtained from women (n = 5, age 27-34 years) after spontaneous labor at term (37-42 weeks gestation) from uncomplicated pregnancies were incubated with [7n-3H]pregnenolone as substrate. Reverse-isotope dilution analysis gave positive identification of [3H]DHEA acetate in all incubations of viable tissues. No such metabolite was evident in control incubations with heat-denatured tissues. Virtually radiochemically pure esters under three recrystallizations were obtained with mean concentrations of between 15787 and 30137 dpm mol(-1) for amnion which was considerably higher than that of chorionic tissues at 4316-5528 dpm mol(-1). The magnitude of elevation in DHEA production by amnion was noted to be between 3.6- and 5.5-fold higher than the corresponding chorion. This study provides evidence that the fetal membranes possess 17-alpha hydroxylase and C-17, 20 lyase activities capable of synthesis of DHEA, an important androgen necessary for aromatization to estrogens in need by the developing fetus.

Amnion↗

Mechanochemical synthesis of nanocrystalline hydroxyapatite from CaO and CaHPO4.

Ceramic hydroxyapatite phase was triggered to occur by high-energy mechanical activation of a dry powder mixture of calcium oxide (CaO) and anhydrous calcium hydrogen phosphate (CaHPO4). A singe-phase hydroxyapatite of high crystallinity was realised by >20 h of mechanical activation without further thermal treatment at high temperatures. The resulting hydroxyapatite powder exhibits an average particle size of approximately 25 nm and a specific surface area of 76.06 m2/g, as measured by multi-point BET technique. It was sintered to a density of 98.20% theoretical density at 1200 degrees C for 2 h.

Calcium Compounds↗

Absence of mutations in the coding regions of follicle-stimulating hormone receptor gene in Singapore Chinese women with premature ovarian failure and polycystic ovary syndrome.

Normal gonadal function is critically dependent on the integrity of pituitary-gonadal axis, where follicle-stimulating hormone (FSH) plays a key role. In the female, FSH is required for follicular growth, estrogen production and oocyte maturation. Its function is mediated by its specific receptor (FSHR), and defective FSHR has been shown to affect folliculogenesis and ovarian function. In this study, we screened the entire coding region of FSHR gene for pathogenic mutations in women with premature ovarian failure (POF) (n = 16) and polycystic ovary syndrome (PCOS) (n = 124) and found no mutations in these patients. Two known polymorphisms, Thr307Ala and Ser680Asn showed similar distributions of the allelic variations and protein isoforms in PCOS and normal control subjects (n = 236). It appears from this study that mutations in the coding regions of FSHR gene are not a causative factor of the above clinical manifestations in Chinese Singapore women.

Adolescent↗

Prognostic value of Y deletion analysis: How reliable is the outcome of Y deletion analysis in providing a sound prognosis?

Y chromosomal microdeletions at the azoospermia factor (AZF) locus have been implicated as one of the major causes of idiopathic male infertility. The availability of intracytoplasmic sperm injection (ICSI) in treating a variety of male infertility has raised the risk of the transmission of Y microdeletions from father to son. In many IVF centres, Y microdeletion analysis has been used as a diagnostic tool for genetic counselling of infertile couples. Presently, the only prognosis that can be derived from Y microdeletion analysis is that the affected male offspring would benefit from proper clinical management of their infertility. Prognoses based on the pattern of Y microdeletions in relation to phenotype are rather subjective and inconclusive because of insufficient data to derive a definitive correlation whose significance can be determined by statistical analysis. Standardization of the number and choice of sequence-tagged sites (STS), whose deletions result in defective spermatogenesis, for the polymerase chain reaction (PCR) analysis of Y microdeletions would enhance its reliability in the interpretation of the results which is crucial for therapeutic decision-making. Furthermore, in-depth understanding of the gene functions in male infertility, especially at the AZF locus, would contribute greatly to the quality of the prognostic value of Y microdeletion analysis.

Chromosome Deletion↗

Ultrastructural observations of enzymatically treated human blastocysts: zona-free blastocyst transfer and rescue of blastocysts with hatching difficulties.

Enzymatic treatment of the zona pellucida to either soften or remove totally the zona before blastocyst transfer has resulted in high implantation rates. The zona is usually completely dissolved after 1.5 min exposure with 10 IU pronase at 37 degrees C. Since there may be concerns that pronase treatment for periods of 1.5 min or longer may cause adverse effects on the trophectoderm (TE) and inner cell mass (ICM), the changes to human blastocysts exposed to different time intervals of pronase were investigated. Of 18 blastocysts exposed to pronase for 1.5 min, the zona was completely dissolved and no changes were observed by light microscopy (LM) or transmission electron microscopy (TEM), compared with 11 naturally hatched untreated blastocysts (controls). In another five blastocysts exposed to pronase for 2 min, no LM changes were observed but subtle TEM changes such as fewer bundles of tonofibrils attached to desmosomes were observed. When three other blastocysts were exposed to pronase for 5 min, the blastocoele collapsed, and the TE cells started to show blebbing under LM. Under TEM, the cytoplasm of TE cells was extensively vacuolated and many TE cells showed cytoplasmic blebbing towards the blastocoele. However, the epithelium was uninterrupted with intact tight junctions and desmosomes. Of a separate group of 44 blastocysts cultured in vitro, 54.5% had hatching difficulties when monitored from day 5 to day 8 and 80% of these could be rescued by removal of the zona with pronase for 1.5 min prior to extensive degeneration taking place. The results confirm that the optimal time for softening or complete removal of the zona before transfer was around 1.5 min and that enzymatic treatment was a safe, non-invasive procedure to remove the zona of blastocysts. The human embryonic TE is a very hardy, robust epithelium that withstands pronase treatment.

Adult↗

Status of peripheral blood natural killer cells in women with recurrent spontaneous abortions and infertility of unknown aetiology.

The aim of this study was to investigate the functional status and immunophenotypic characteristics of natural killer (NK) cells in women who suffer recurrent spontaneous abortions (RSA) or have infertility of unknown aetiology. Peripheral blood mononuclear cells (PBMC) were obtained from 40 study patients and 13 normal healthy multiparous controls. NK cells were identified using anti-CD56 and anti-CD16 monoclonal antibodies (mAb). The expression of CD69, CD25, CD122, CD30, CD154, CD128 and CD94 on NK cells was detected using specific mAb and analysed by flow cytometry. CD69 expression on NK cells after ED(27) human trophoblast cell line co-culture with PBMC was also investigated. A significant increase in CD69 expression on CD56(+) NK cells was demonstrated in women with RSA (P < 0.005) and infertility (P < 0.05) as compared with that of normal controls. Conversely, CD94 expression was significantly decreased in women with RSA (P < 0.005) and infertility (P < 0.05) in comparison with that of controls. Increased CD69 expression on NK cells was induced after 24 h co-culture with ED(27). In conclusion, peripheral blood NK cells of women with RSA and infertility of unknown aetiology have higher proportions of activated NK cells in vivo. Unbalanced CD69 and CD94 expression may explain the underlying pathology.

Abortion, Habitual↗

Expression profiles of interleukin-15 in early and late gestational human placenta and in pre-eclamptic placenta.

The presence of interleukin-15 (IL-15) mRNA in human placenta has been demonstrated previously. The present study was undertaken to investigate the expression profiles of IL-15 mRNA and protein in early and late gestational placental tissues, and also the effect of labour on its production. Levels of placental IL-15 expression were also determined in patients presenting with pre-eclampsia. An explant culture system was used to study the release of immunoreactive IL-15 by the placental tissues. Enzyme-linked immunosorbent assays were employed to quantify concentrations in the culture medium. The results showed that placental tissues from all groups released immunoreactive IL-15 into the culture medium. Moreover, the level of secretion by the term placental tissues was much higher than that by first trimester tissues. The presence of labour at term resulted in a further increase in placental IL-15 production. Reverse transcription-polymerase chain reaction (RT-PCR) was used to demonstrate the expression of IL-15 mRNA in these tissues. The results confirmed the expression of IL-15 in placenta from all the groups and the mRNA levels in the samples was highly correlated with the respective protein concentrations. Levels of both IL-15 mRNA and protein were significantly reduced in the pre-eclamptic placental tissue compared with the normal controls. The present study suggests an important role for this novel cytokine in human pregnancy.

Culture Media↗

Early onset methotrexate-induced pancytopenia and response to G-CSF: a report of two cases.

Methotrexate (MTX) is one of the most widely used antirheumatic drugs for the treatment of rheumatoid arthritis. Whereas the hepatotoxicity of methotrexate is well recognized, the hematologic toxicity, namely, pancytopenia, is still a concern and is potentially fatal. We report two cases of early-onset methotrexate-induced pancytopenia that were successfully treated with granulocyte colony-stimulating factor (G-CSF). The pancytopenia improved with 3 days of administration. A review of the literature revealed at least 146 reported cases of MTX-induced pancytopenia. Significant risk factors for myelotoxicity included renal impairment, infection, and hypoalbuminemia. Successful management includes prompt discontinuation of MTX, intravenous folinic acid, high-dose steroids and, as in our case, G-CSF.

Journal Article↗

Oxytocics reverse the tocolytic effect of glyceryl trinitrate on the human uterus.

OBJECTIVES: To investigate the effect of glyceryl trinitrate on isolated human pregnant uterine strips and whether the uterine relaxation induced by glyceryl trinitrate could be reversed by oxytocics used in current clinical practice. DESIGN: In vitro pharmacological study. SETTING: Department of Obstetrics & Gynaecology, National University of Singapore, National University Hospital. PARTICIPANTS: Eighteen women who delivered by caesarean section at term. METHODS: Myometrial strips were preloaded with an initial tension of 1.5g in organ baths containing Krebs-Henseleit solution which was aerated with oxygen in 5% carbon dioxide and maintained at 37 degrees C, pH 7.4. The effect of glyceryl trinitrate was studied in strips displaying regular spontaneous contractions. The ability of oxytocin, ergometrine or prostaglandin F2alpha to stimulate uterine contractions was assessed in strips where uterine activity was significantly inhibited by glyceryl trinitrate. RESULTS: Glyceryl trinitrate reduced the amplitude and frequency of spontaneous uterine contractions in a concentration-dependent manner, although the sensitivity of the myometrial strips varied considerably from one specimen to another. The concentration of glyceryl trinitrate producing complete inhibition of myometrial contractions ranged from 44-705 microM. In the presence of glyceryl trinitrate which markedly depressed spontaneous contractions, oxytocin (20 mU/mL), ergometrine (6.15 microM) and prostaglandin F2alpha (6.15 microM) were capable of reversing the uterine activity to either higher than or the untreated level of contractility. CONCLUSIONS: This study demonstrates that glyceryl trinitrate is a potent uterine relaxant in vitro and that the tocolytic effect could be reversed with ease by oxytocics.

Dinoprost↗