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Biomedical subjects

Y P Chan

Publications and source records attributed to Y P Chan.

15 recordsLinked to original sources

The significance of LMO2 expression in the progression of prostate cancer.

LIM domain only 2 (LMO2) proteins are important regulators in determining cell fate and controlling cell growth and differentiation. This study has investigated LMO2 expression in human prostatic tissue specimens, prostate cancer cell lines, and xenografts; and has assessed the possible role and mechanism of LMO2 in prostate carcinogenesis. Immunohistochemical analysis on a tissue microarray consisting of 91 human prostate specimens, including normal, prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, and invasive carcinoma, revealed that overexpression of LMO2 was significantly associated with advanced tumour stage, as measured by Gleason score (p = 0.012), as well as with the development of distant metastasis (p = 0.018). These data were supported by quantitative real-time PCR experiments, where LMO2 mRNA levels were found to be significantly higher in prostate tumour specimen than in normal epithelium (p = 0.037). The expression of LMO2 in cell lines and xenografts representing androgen-dependent (AD) and androgen-independent (AI) prostate cancer stages was further studied. Consistent with the in vivo data, LMO2 mRNA and protein were found to be overexpressed in the more aggressive AI cells (PC3, DU145, and AI CWR22 xenografts) compared with less aggressive AD cells (LNCaP and AD CWR22 xenografts). Furthermore, stable introduction of LMO2 into LNCaP cells conferred enhanced cell motility and invasiveness in vitro, accompanied by down-regulation of E-cadherin expression. Taken together, these findings provide the first evidence to support the hypothesis that LMO2 may play an important role in prostate cancer progression, possibly via repression of E-cadherin expression.

Adaptor Proteins, Signal Transducing↗

Mapping of domains responsible for nucleocapsid protein-phosphoprotein interaction of Henipaviruses.

Hendra virus (HeV) and Nipah virus (NiV) are members of a new genus, Henipavirus, in the family paramyxoviridae. Each virus encodes a phosphoprotein (P) that is significantly larger than its counterparts in other known paramyxoviruses. The interaction of this unusually large P with its nucleocapsid protein (N) was investigated in this study by using recombinant full-length and truncated proteins expressed in bacteria and a modified protein-blotting protein-overlay assay. Results from our group demonstrated that the N and P of both viruses were able to form not only homologous, but also heterologous, N-P complexes, i.e. HeV N was able to interact with NiV P and vice versa. Deletion analysis of the N and P revealed that there were at least two independent N-binding sites on P and they resided at the N and C termini, respectively. Similarly, more than one P-binding site was present on N and one of these was mapped to a 29 amino acid (aa) C-terminal region, which on its own was sufficient to interact with the extreme C-terminal 165 aa region of P.

Amino Acid Sequence↗

Complete nucleotide sequences of Nipah virus isolates from Malaysia.

We have completely sequenced the genomes of two Nipah virus (NiV) isolates, one from the throat secretion and the other from the cerebrospinal fluid (CSF) of the sole surviving encephalitic patient with positive CSF virus isolation in Malaysia. The two genomes have 18246 nucleotides each and differ by only 4 nucleotides. The NiV genome is 12 nucleotides longer than the Hendra virus (HeV) genome and both genomes have identical leader and trailer sequence lengths and hexamer-phasing positions for all their genes. Both NiV and HeV are also very closely related with respect to their genomic end sequences, gene start and stop signals, P gene-editing signals and deduced amino acid sequences of nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, glycoprotein and RNA polymerase. The existing evidence demonstrates a clear need for the creation of a new genus within the subfamily Paramyxovirinae to accommodate the close similarities between NiV and HeV and their significant differences from other members of the subfamily.

Base Sequence↗

Acute confusion secondary to pneumocephalus in an elderly patient.

PRESENTATION: an 83-year-old man was admitted to hospital with acute confusion 3 days after a direct flight from Australia. OUTCOME: computed tomography (CT) brain scan and magnetic resonance imaging head scan revealed the cause to be pneumocephalus, apparently the result of barotrauma caused by Valsalva manoeuvres when he attempted to unblock his nose during the flight. After 5 days of nursing in the vertical position the patient's Abbreviated Mental Score returned to normal. A CT brain scan 6 weeks later showed complete resolution of the pneumocephalus.

Acute Disease↗

A PC-based surgical simulator for laparoscopic surgery.

Surgical simulators for minimally invasive surgery have been developing in the 1990s. Most of them use high-end UNIX workstations for real-time simulation of complex human organ models. Only few of them have input devices with force feedback. Recently, personal computer technologies have made real-time display of relatively complex models feasible. We are developing an Intel-based laparoscopic surgical simulator that provides near real-time intuitive interaction between the trainee and simulated models of human organs. The surgical simulator has a prototypical scenario of cholecystectomic surgery. It can interactively simulate the deformation and cutting of cystic duct and vein. In addition, a set of input devices with force feedback has been designed and tested to imitate the manipulation of surgical instruments. The input device has five degrees of freedom and three of them are driven by DC motors to produce force feedback.

Cholecystectomy↗

Quantitation of homoharringtonine in plasma by high-performance liquid chromatography with amperometric detection.

A high-performance liquid chromatographic procedure was developed for the quantitation of homoharringtonine in plasma. Harringtonine was used as an internal standard, and 1 ml of sample was required. The single-step extraction with dichloromethane resulted in almost 100% recovery for homoharringtonine and harringtonine. Analysis was performed on a reversed-phase CN column with amperometric detection. Chromatography was completed in 12 min. At an oxidation potential of +1.0 V, the detection limit was 1 ng/ml at a signal-to-noise ratio of 2. The mean analytical recovery for homoharringtonine was 99.5%. The within-run precision and between-run precision were both less than 11%. The method is equally applicable for plasma or serum, and it has been demonstrated to be applicable for study of the pharmacokinetics of homoharringtonine in patients suffering from acute non-lymphocytic leukaemia.

Alkaloids↗

Pre-operative parenteral nutrition in patients with oesophageal cancer: a prospective, randomised clinical trial.

A prospective randomised clinical trial was conducted to examine the efficacy of 2 weeks pre-operative parenteral nutrition (PPN) for the prevention of complications following surgery for oesophageal cancer. Forty patients were studied, the diet of twenty being supplemented by pre-operative parenteral nutrition. There were no significant differences in age, nutritional status, tumour staging and histology between the two groups of patients. The use of PPN resulted in a significant gain in body weight and nitrogen but failed to produce an overall reduction in post-operative morbidity and mortality rates. However patients receiving PPN exhibited two types of changes in serum albumin levels. Those with a fall in serum albumin levels associated with an increase in body weight (indicating an expansion of extracellular volume) had a significantly higher incidence of post-operative pulmonary complications than the group exhibiting a rise in serum albumin levels concomitant with increase in body weight. These data suggested that two weeks PPN might not be adequate in certain patients and a longer period of PPN is required. They also show no clinical benefit from the routine use of pre-operative parenteral nutrition in all patients, but do not exclude benefit in selected groups.

Journal Article↗

Simultaneous quantitation of catecholamines and O-methylated metabolites in urine by isocratic ion-pairing high-performance liquid chromatography with amperometric detection.

A simple high-performance liquid chromatographic procedure was developed for the simultaneous determination of catecholamines and metanephrines in urine. One-step sample preparation was achieved with Bio-Rex 70 ion-exchange resin. The extract was assayed on a C18 reversed-phase column. Dihydroxybenzylamine was used as an internal standard. The eluent was monitored by an electrochemical detector with an oxidation potential of +0.85 V. The use of 1-heptanesulphonic acid in the mobile phase permitted the separation of norepinephrine, epinephrine, dopamine, normetanephrine and metanephrine in a single chromatogram. The corresponding detection limits were 5, 9, 14, 10 and 30 nmol/l, respectively. For the between-day precision, the coefficients of variation at physiological and pathological concentrations were less than 11%. Compounds with similar chemical structures and drugs commonly prescribed for the treatment of hypertension were assayed and found not to cause interferences in the chromatogram. The assay is reliable and is suitable for the analysis of clinical specimens. Reference values were established for normotensive Chinese patients with no neurological or endocrine disorders and also for patients suffering from essential hypertension.

Adrenal Gland Neoplasms↗

Single-dose pharmacokinetics of ceftriaxone in healthy Chinese adults.

The pharmacokinetics of ceftriaxone were investigated in six healthy mainland Chinese adults (four males and two females). A single 1.0-g dose was administered intravenously or intramuscularly in a two-way crossover design. Plasma and saliva samples were collected on 11 occasions between 0 and 36 h after dosing. Ceftriaxone was not detected in any saliva samples. The mean volume of distribution and mean elimination half-life of ceftriaxone in plasma were 8.5 liters and 8.1 h, respectively. The mean total body clearance after intravenous administration was 0.68 liter/h. The mean Tmax and Cmax after intramuscular injection were 1.4 h and 131 micrograms/ml, respectively. The area under the plasma concentration-time curves after intravenous and intramuscular administrations were 1,507 and 1,493 micrograms X h/ml, respectively. The bioavailability for a 1.0-g intramuscular dose of ceftriaxone was calculated to be 100%. These pharmacokinetic parameters for ceftriaxone in healthy Chinese adults were very similar to those previously reported in the literature. Thus, ceftriaxone may be administered to treat Chinese patients without any major modification in the standard dosing regimen.

Adult↗

Methylphenidate hydrochloride given with or before breakfast: II. Effects on plasma concentration of methylphenidate and ritalinic acid.

Methylphenidate HCl (Ritalin) is often prescribed for the treatment of hyperactivity and is usually administered orally 30 minutes to 1 hour before meals, based on an assumption that meals may interfere with the absorption or metabolism of the drug. Seven boys who were taking methylphenidate regularly for the treatment of hyperactivity were hospitalized and given their established dose of the drug intravenously or orally, either with breakfast or in a fasted state. Blood samples were taken to determine the pharmacokinetics of the drug in each condition. Few differences between the "fed" and "fasted" states were noted, but the statistically significant differences indicated that meals accelerate rather than impede the absorption of methylphenidate.

Adolescent↗

Liquid-chromatographic analysis for methylphenidate (Ritalin) in serum.

We describe a "high performance" liquid chromatographic method for quantitating methylphenidate in serum. The internal standard, 4,5-diphenylimidazole, and serum or plasma sample are extracted in chloroform, evaporated, and redissolved in 20 mmol/L potassium phosphate (pH 3.5)/high-purity acetonitrile, 80/20 by vol. A centrifuged aliquot is chromatographed on mu-Bondapak C-18 with the phosphate/acetonitrile solvent as mobile phase, a flow rate of 1.6 mL/min, and a column temperature of 40 degrees C. Absorbances are read at 192 nm. This method reliably measures concentrations greater than 20 micrograms/L and has analytical recoveries of 74%.

Child↗

Effect of 7,12-dimethylbenz(a)anthracene on the binding of aminoacyl transfer RNA in rat liver.

Homogenates of the liver of female rats obtained 2 or 7 days or 3 months after the i.v. injection of 7,12-dimethylbenz(a)anthracene were used to prepare ribosomes and postmicrosomal supernatant fractions and to prepare 0.5 M KCl salt wash fractions of the 40 S ribosomal subunits. The activity of the ribosomes was unchanged by 7,12-dimethylbenz(a)anthracene. The activity of the supernatant preparation, which contained limiting amounts of Elongation Factor 1 relative to Elongation Factor 2, in peptide synthesis was significantly increased 2 days not 7 days after the injection. Evidence was obtained that this increase was due to increased activity in binding phenylalanyl transfer RNA. The factor-dependent binding of methionyl transfer RNAfMet to control rat liver ribosomes was also markedly increased 2 days but not 7 days after the injection. The liver of animals that bore mammary tumors 3 months after 7,12-dimethylbenz(a)anthracene injection also showed an increase in binding both of the aminoacyl transfer RNA species. The results are discussed in relation to the induction of liver drug-metabolizing enzymes and to liver regeneration.

9,10-Dimethyl-1,2-benzanthracene↗