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Biomedical subjects

K L Tan

Publications and source records attributed to K L Tan.

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

Dynamic holography for optical interconnections. II. Routing holograms with predictable location and intensity of each diffraction order.

An analysis of dynamic phase-only holograms, described by fractional notation and recorded onto a pixelated spatial light modulator (SLM) in a reconfigurable optical beam-steering switch, is presented. The phase quantization and arrangement of the phase states and the SLM pixelation and dead-space effects are decoupled, expressed analytically, and simulated numerically. The phase analysis with a skip-rotate rule reveals the location and intensity of each diffraction order at the digital replay stage. The optical reconstruction of the holograms recorded onto SLM's with rectangular pixel apertures entails sinc-squared scaling, which further reduces the intensity of each diffraction order. With these two factors taken into account, the highest values of the nonuniform first-order diffraction efficiencies are expected to be 33%, 66%, and 77% for two-, four-, and and eight-level one-dimensional holograms with a 90% linear pixel fill factor. The variation of the first-order diffraction efficiency and the relative replay intensities were verified to within 1 dB by performing the optical reconstruction of binary phase-only holograms recorded onto a ferroelectric liquid crystal on a silicon SLM.

Journal Article↗
PubMed2000

Carbon nanotubes: a future material of life.

The synthesis and applications of carbon nanotubes, a new form of crystalline carbon, are reviewed. In particular, the results obtained in the authors' laboratory are summarized, including the preparation of highly crystalline multi-walled carbon nanotubes; also discussed are the valence band and core level structures, the nonlinear optical limiting behavior, the band gap measurement, and the hydrogen uptake by carbon nanotubes, which has been greatly enhanced by alkali-doping.

Carbon↗
PubMed2000

Surface modification of poly(tetrafluoroethylene) films via grafting of poly(ethylene glycol) for reduction in protein adsorption.

Poly(tetrafluoroethylene) (PTFE) films with surface grafted poly(ethylene glycol) (PEG) chains were prepared by two methods: (1) UV-induced graft copolymerization of methoxy poly- (ethylene glycol) monomethacrylate (PEGMA) onto the plasma-pretreated PTFE films; and (2) coupling of the hydroxyl groups of PEG via ester linkages with the carbonyl chloride groups which were introduced onto the acrylic acid (AAc) graft-copolymerized PTFE surface through reaction with thionyl chloride (SOCl2). The UV-induced graft copolymerization of PEGMA onto the plasma-pretreated PTFE film was explored with different macromonomer concentrations and different UV graft copolymerization time. The coupling reaction, on the other hand, was explored with PEG of different molecular weights. The surface microstructures and compositions of the PEG-modified PTFE films from both processes were characterized by contact angle, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) measurements. In general, higher macromonomer concentration and longer UV graft copolymerization time led to a higher graft yield for the UV-induced graft copolymerization with PEGMA. Contact angle measurements revealed that the hydrophilicity of the PTFE film surface was greatly enhanced by the grafting of the PEG chains. The PTFE surface with a high density of grafted PEG was very effective in preventing bovine serum albumin adsorption.

Adsorption↗
PubMed2000

Hard metal lung disease--the first case in Singapore.

INTRODUCTION: We report the first case of hard metal lung disease in Singapore and the occupational investigative work and control measures that were undertaken. CLINICAL PICTURE: A 38-year-old machinist in the tool manufacturing industry presented with exertional dyspnoea and cough. Chest X-ray revealed bilateral reticulonodular infiltrates with honeycombing. High resolution computed tomography scan of the thorax confirmed the presence of interstitial fibrosis. Open biopsy of the lung showed features of pneumoconiosis. Particle induced X-ray emission (PIXE) analysis, a relatively new elemental analysis technique, performed on the lung biopsy specimen confirmed the presence of tungsten and titanium; and he was diagnosed to have hard metal lung disease. Microbiologic, serologic and histologic investigations excluded an infective cause. Serial pulmonary function tests on follow-up showed no progression. He presented with haemoptysis 10 months later and was diagnosed to have tuberculosis on the basis of positive sputum and bronchoalveolar lavage cultures for Mycobacterium tuberculosis complex. TREATMENT: Preventive measures and permanent transfer to non-cobalt work were instituted. OUTCOME: The interstitial fibrosis appears to have stabilised. CONCLUSION: The diagnosis of hard metal lung disease must be considered in a worker exposed to cobalt presenting with interstitial fibrosis.

Adult↗
PubMed1999

Intermittent hypoxaemia without orthodeoxia due to right-to-left shunting related to an elongated aorta.

An elderly woman presented with unexplained, intermittent hypoxaemia unrelated to posture. Subsequent investigations revealed intermittent and variable right-to-left interatrial shunting through a patent foramen ovale in the presence of normal pulmonary arterial and intracardiac pressures, caused by right atrial compression from a horizontal, elongated ascending aorta. Surgical closure of the foramen resulted in marked clinical improvement.

Aged↗
PubMed1998

Conversion of bovine pancreatic DNase I to a repair endonuclease with a high selectivity for abasic sites.

Bovine pancreatic deoxyribonuclease I (DNase I) is a nuclease of relatively low specificity which interacts with DNA in the minor groove. No contacts are made between the protein and the major groove of the nucleic acid. DNase I is structurally homologous to exonuclease III, a DNA-repair enzyme with multiple activities. One of the main differences between the two enzymes is the presence of an additional alpha-helix in exonuclease III, in a position suggestive of interaction with the major groove of DNA. Recombinant DNA techniques have been used to add 14 amino acids, comprising the 10 amino acids of the exonuclease III alpha-helix flanked by a glycine rich region, to DNase I. The polypeptide has been inserted after serine 174, an amino acid on the surface of DNase I corresponding to the location of the extra alpha-helix in exonuclease III. The recombinant protein, DNase-exohelix, has been purified and its catalytic activities towards DNA investigated. The recombinant protein demonstrated a high selectivity for endonucleolytic cleavage at abasic sites in DNA, a property of exonuclease III but not native DNase I. Thus the insertion of 14 amino acids at Ser174, converts DNase I to an exonuclease III-like enzyme with DNA-repair properties.

Animals↗
PubMed1998

[Frontotemporal dementia in a young woman with apparent schizophrenia].

In a woman aged 35 who for the last 5 years had been suffering from conduct disorders, especially kleptomania, compulsive cleaning behaviour and affective neglect of her children, psychodiagnostic examination initially suggested a delusional disorder. In view of the gradual aggravation of bizarre behaviour, the diagnosis 'schizophrenic psychosis of the hebephrenic type' was made; supplementary examination revealed no abnormalities. Finally, in view of the ununderstood and progressive behavioural changes, the diagnosis was reconsidered; on the basis of clinical findings, SPECT examination and results of repeated CT of the brain, the diagnosis of 'frontotemporal dementia, type Pick' was made.

Adult↗
PubMed1998

Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site.

BACKGROUND: Glutathione S-transferases (GSTs) comprise a multifunctional group of enzymes that play a critical role in the cellular detoxification process. These enzymes reduce the reactivity of toxic compounds by catalyzing their conjugation with glutathione. As a result of their role in detoxification, GSTs have been implicated in the development of cellular resistance to antibiotics, herbicides and clinical drugs and their study is therefore of much interest. In mammals, the cytosolic GSTs can be divided into five distinct classes termed alpha, mu, pi, sigma and theta. The human theta class GST, hGST T2-2, possesses several distinctive features compared to GSTs of other classes, including a long C-terminal extension and a specific sulfatase activity. It was hoped that the determination of the structure of hGST T2-2 may help us to understand more about this unusual class of enzymes. RESULTS: Here we present the crystal structures of hGST T2-2 in the apo form and in complex with the substrates glutathione and 1-menaphthyl sulfate. The enzyme adopts the canonical GST fold with a 40-residue C-terminal extension comprising two helices connected by a long loop. The extension completely buries the substrate-binding pocket and occludes most of the glutathione-binding site. The enzyme has a purpose-built novel sulfate-binding site. The crystals were shown to be catalytically active: soaks with 1-menaphthyl sulfate result in the production of the glutathione conjugate and cleavage of the sulfate group. CONCLUSIONS: hGST T2-2 shares less than 15% sequence identity with other GST classes, yet adopts a similar three-dimensional fold. The C-terminal extension that blocks the active site is not disordered in either the apo or complexed forms of the enzyme, but nevertheless catalysis occurs in the crystalline state. A narrow tunnel leading from the active site to the surface may provide a pathway for the entry of substrates and the release of products. The results suggest a molecular basis for the unique sulfatase activity of this GST.

Binding Sites↗
PubMed1998

Preliminary X-ray crystallographic studies of a newly defined human theta-class glutathione transferase.

Human theta-class glutathione S-transferases (GST's) appear to play a critical role in the metabolism of a variety of environmental pollutants but in some cases the products of the reaction are carcinogenic. Crystals of a human theta-class GST, namely hGSTT2-2, have been grown from polyethylene glycol by the hanging-drop vapour-diffusion method. The crystals belong to the trigonal space group P3121 with cell dimensions of a = b = 94.0 and c = 120.5 A. They contain two monomers in the asymmetric unit and diffract to 3.0 A resolution.

Crystallization↗
PubMed1998

Decreased response to phototherapy for neonatal jaundice in breast-fed infants.

OBJECTIVE: To evaluate the efficacy of phototherapy for nonhemolytic hyperbilirubinemia in breast-fed and formula-fed infants and infants receiving formula and breast milk. DESIGN: Prospective study. SETTING: Nursery for healthy infants. METHOD: Full-term healthy infants with nonhemolytic hyperbilirubinemia (bilirubin concentration, >255 micromol/L [14.9 mg/dL] or 222 micromol/L [13.0 mg/dL] at ages younger than 48 hours) were treated with conventional phototherapy by using daylight fluorescent lamps. Three groups of infants were studied: group 1, formula-fed infants; group 2, breast-fed infants; and group 3, infants receiving formula and breast milk. All patterns of feeding started at birth. Phototherapy was terminated only when bilirubin concentrations had decreased to less than 185 micromol/L (10.8 mg/dL); the minimum exposure period was 24 hours. RESULTS: A total of 163 infants were studied: group 1, 79; group 2, 34; and group 3, 50. The age at the start of exposure was comparable in all groups. The mean+/-SD weight loss as a percentage of birth weight was as follows: group 1, 2.8%+/-5.0%; group 2, 6.1%+/-3.4%; and group 3, 3.2%+/-2.6%. The duration of exposure to phototherapy was as follows: group 1, 54.1+/-20.8 hours; group 2, 64.6+/-25.1 hours; and group 3, 54.9+/-21.5 hours; the 24-hour rate of decrease in the bilirubin concentration was as follows: group 1, 18.6%+/-11.7%; group 2, 17.1%+/-9.6%; and group 3, 22.9%+/-9.4%. The overall rate of decrease in the bilirubin concentration for the duration of exposure to phototherapy was as follows: group 1, 0.8%+/-0.3% per hour; group 2, 0.6%+/-0.3% per hour; and group 3, 0.8%+/-0.3% per hour. Weight loss at the start of phototherapy was significantly greater in group 2 compared with group 1 (P<.001) and group 3 (P<.001), although the hemoglobin and hematocrit values were comparable. The duration of exposure to phototherapy was not significantly different in the 3 groups (P=.06); however, the duration of exposure of group 2 infants was 10 hours more than that of the other 2 groups. The 24-hour rate of decrease in the bilirubin concentration in group 3 was significantly better than that of group 2 (P = .007) and group 3 (P = .02); the rates of decrease for groups 2 and 3 were similar (P = .52). The overall rate of decrease in the bilirubin concentration during the duration of exposure to phototherapy in group 2 was significantly less than that of group 1 (P = .002) and group 3 (P<.001); the rates for groups 1 and 3 were similar (P = .35). The postexposure rebound bilirubin concentrations were comparable in all groups during the first 2 days; however, the duration of moderate jaundice in group 2 was more prolonged. CONCLUSIONS: The response to phototherapy of group 2 infants was significantly slower than that of group 3 and group 1 infants; this response was still of adequate efficacy. The addition of formula to the feedings for totally breast-fed infants, without suspension of breast-feeding, would enhance the efficacy of phototherapy and reduce exposure time.

Bilirubin↗
PubMed1997

Homology model for the human GSTT2 Theta class glutathione transferase.

A tertiary model of the human GSTT2 Theta class glutathione transferase is presented based on the recently solved crystal structure of a related thetalike isoenzyme from Lucilia cuprina. Although the N-terminal domains are quite homologous, the C-terminal domains share less than about 20% identity. The model is used to consolidate the role of Ser 11 in the active site of the enzyme as well as to identify other residues and mechanisms of likely catalytic importance. The T2 subfamily of theta class enzymes have been shown to inactivate reactive sulfate esters arising from arylmethanols. A possible reaction pathway involving the conjugation of glutathione with one such sulfate ester, 1-menaphthyl-sulfate, is described. It is also proposed that the C-terminal region of the enzyme plays an important role in allowing substrate access to the active site.

Amino Acid Sequence↗
PubMed1997

Efficacy of bidirectional fiber-optic phototherapy for neonatal hyperbilirubinemia.

OBJECTIVE: To evaluate the efficacy of fiber-optic phototherapy using the standard Ohmeda Biliblanket, a large version, double standard Biliblankets, and conventional phototherapy using daylight fluorescent lamps in full-term, healthy infants with nonhemolytic hyperbilirubinemia. METHODS: Full-term, healthy infants with nonhemolytic hyperbilirubinemia (bilirubin concentration, >255 micromol/L or 222 micromol/L at <48 hours of age) were allocated randomly to one of four modes of phototherapy: standard fiber-optic mat (Ohmeda Biliblanket), a large version, double standard Biliblankets, and conventional phototherapy. Bilirubin levels were monitored every 12 hours. Exposure was stopped when bilirubin levels were less than 185 micromol/L, the minimum duration being 24 hours. RESULTS: A total of 171 infants were studied; 42 were exposed to standard fiber-optic phototherapy, 43 to large fiber-optic phototherapy, 42 to double-fiber-optic phototherapy, and 44 to conventional phototherapy. Durations of exposure were 87.05 +/- 6.09 (SEM), 82.57 +/- 5.84, 64.85 +/- 5.43, and 62.61 +/- 3.74 hours, respectively; the 24-hour decline rates were 10.26% +/- 1.84%, 14. 50% +/- 1.53%, 21.82% +/- 1.71%, and 19.00% +/- 1.65%, respectively; the overall decline rates over the whole exposure period were 0.47% +/- 0.03%, 0.52% +/- 0.04%, 0.71% +/- 0.05%, and 0.75% +/- 0.04% per hour, respectively. The efficacy of double-fiber-optic phototherapy and conventional phototherapy was similar and significantly better than that of the large fiber-optic mat and the standard fiber-optic mat in duration, 24-hour decline rate, and overall decline rate. The large mat was slightly better than the standard-size mat with regard to 24-hour decline rate and overall decline rate, but this difference was not significant. Failure of phototherapy occurred only in the large fiber-optic mat group (3 of 43) and the standard fiber-optic mat group (4 of 42); none occurred in the other two groups, but differences not statistically significant. The nursing personnel were more comfortable with single fiber-optic phototherapy, which caused no initial disturbance to the swaddled infants as did conventional phototherapy, but found double-fiber-optic phototherapy difficult to use. CONCLUSION: For efficacy of fiber-optic phototherapy in full-term infants to be comparable to that of our conventional phototherapy, the light dose of the standard mats needs to be doubled.

Analysis of Variance↗
PubMed1997

Chylothorax: case report and review of literature.

Chylothorax is a relatively uncommon condition. We report a case of a 53-year-old Chinese man with chylothorax who presented with cough, breathlessness, loss of weight and generalised lymphadenopathy. He was initially diagnosed as having tuberculosis based on histology and cultures of the cervical lymph node. However, immunophenotyping of the pleural fluid by flow cytometry showed the presence of a monoclonal B cell population with Kappa light chain expression suggesting an underlying lymphoproliferative disorder. A repeat lymph node biopsy showed malignant lymphoma (follicular small cleaved type). In spite of aggressive measures which included bilateral tube thoracostomy drainage, a low fat diet, medium chain triglyceride diet, total parenteral nutrition, chemotherapy and mediastinal irradiation, his chylothorax persisted. Hence, we report a patient with persistent chylothorax and generalised lymphadenopathy who was subsequently diagnosed to have concurrent tuberculosis and malignant lymphoma. The literature on chylothorax is reviewed.

Biopsy↗
PubMed1997

An epidemiological study of developmental dysplasia of the hip in infants in Singapore.

The incidence of congenital dislocation of the hip (CDH) in Singapore and Malaysia has been reported as being lower than in the West. In our hospital, we have seen an increasing number of congenital hip dislocation as well as dysplastic hips. We undertook a prospective study from December 1989 to December 1994 of 20,000 live births. The neonates were all screened by a consultant neonatologist and the findings were confirmed by a consultant paediatric orthopaedic surgeon. All babies had plain X-rays at 3 months and an acetabular index (AI) of 30 degrees or more was considered dysplastic. All babies with positive signs were followed up for 1 year and again had radiographs taken at 1 year. Comparison of plain X-rays and ultrasound assessment in a subgroup of 130 neonates showed that 64% of patients with AI > 20 degrees had hip dysplasia by ultrasonographic (alpha angle < 60 degrees) The incidence of dysplastic hips was 16.8 per 1000 live births. The overall incidence of neonates with dislocated hips was 4.7 per 1000 live births. The Malays were most affected with an incidence of 5.4 per 1000 live births. The incidence of developmental dysplasia of the hip in Singapore is higher than previously reported, with the Malays having the highest incidence. A significant number of babies with clicking hips have radiological evidence of acetabular dysplasia (AI > 30 degrees). One-third of the babies' hips were still dysplastic at 1 year of age. A well-organised screening programme with experienced examiners has proved to be useful in making early and accurate clinical diagnosis.

Female↗
PubMed1997

Vocal cord dysfunction: two case reports.

Vocal cord dysfunction is an uncommon condition characterised by adduction of vocal cords that can masquerade as or coexists with bronchial asthma. The glottic dysfunction is due to a functional (non-organic) cause. If unrecognised, incorrect diagnosis may result in patients being unnecessarily treated as refractory or severe asthma with high doses of corticosteroid. This may result in unwarranted steroid toxicity. Clues that should raise clinical suspicion to the diagnosis of vocal cord dysfunction include lack of response to bronchodilators, poor reproducibility of spirometric indices due to inconsistent effort and truncation of the inspiratory limb of the flow-volume loop. Definitive diagnosis is made by direct visualisation of the vocal cords during an attack. We report two patients with vocal cord dysfunction and review the literature on this disorder.

Adolescent↗
PubMed1997

Spontaneous corneal perforation in premature infants.

Spontaneous corneal perforation in premature infants not due to birth trauma is a rare event, with only 8 cases reported in the literature. We recently encountered a case of spontaneous corneal perforation in an extremely premature infant born at 26 weeks of gestation. The mechanism leading to this event was corneal exposure resulting in corneal epithelial defect. Clinical evidence of secondary infection ensued and this led to cornea thinning, descemetocoele formation and subsequent perforation with extrusion of intraocular contents. Although other mechanisms were responsible in the previously reported cases, we feel that exposure keratopathy leading to this complication poses a potential hazard to all premature infants. An awareness among care givers of this potential complication together with avoidance of exposure keratopathy in this group of patients is paramount in preventing this visually catastrophic event.

Cornea↗
PubMed1996

Mutagenesis of the active site of the human Theta-class glutathione transferase GSTT2-2: catalysis with different substrates involves different residues.

The role of serine-11 in the catalytic mechanism of recombinant human GSTT2-2 was examined by site-directed mutagenesis. Amino acid sequence comparison of the Theta-class isoenzymes has identified a conserved serine residue in the N-terminal domain [Wilce, Board, Feil and Parker (1995) EMBO J. 14, 2133-2143]. This conserved serine has been implicated in the activation of the enzyme-bound glutathione [Board, Coggan and Parker (1995) Biochem. J. 311, 247-250]. Mutating the equivalent serine (residue 11) of GSTT2-2 to Ala, Thr or Tyr abolished the catalytic properties of GSTT2-2 with cumene hydroperoxide and ethacrynic acid as second substrate. However, with l-menaphthyl sulphate (MSu) as the second substrate, the specific activity of the S11A mutant was doubled, while the S11T mutant retained half the wild-type activity and the S11Y mutant was inactive. The role of Ser-11 in catalysis seems to vary with different second substrates. In the substitution reaction with MSu, GSTT2-2 activity appears to depend on the size of the Ser-11 replacement rather than the presence of a side-chain hydroxy group. In addition, the reaction rate appears to be a function of pH, and there is no non-enzymic reaction even at high pH. We demonstrated that a reaction between MSu and an alternative thiol such as L-cysteine or 2-mercaptoethanol can take place in the presence of S-methylglutathione and GSTT2-2. We propose that the catalytic activity of GSTT2-2 with MSu is preceded by a conformational or charge modification to the enzyme upon the binding of glutathione or S-methylglutathione. This is followed by the binding of MSu and the subsequent removal of the sulphate group, giving rise to the carbonium ion of l-methylnaphthelene as the electrophile that reacts with the nucleophilic species. The reaction mechanism of GSTT2-2 with MSu may represent a novel function of GSTT2-2 as a glutathione-dependent sulphatase.

Benzene Derivatives↗