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Biomedical subjects

W K Chan

Publications and source records attributed to W K Chan.

154 records · Page 9Linked to original sources
PubMedDate not supplied

Mechanisms of regulation of liver fatty acid-binding protein.

Liver fatty acid-binding protein (L-FABP) expression is modulated by developmental, hormonal, dietary, and pharmacological factors. The most pronounced induction is seen after treatment with peroxisome proliferators, which induce L-FABP coordinately with microsomal cytochrome P-450 4A1 and the enzymes of peroxisomal fatty acid beta-oxidation. These effects of peroxisome proliferators may be mediated by a receptor which has been shown to be activated by peroxisome proliferators in mammalian cell transfection studies. However, the peroxisome proliferators tested thus far do not bind to this receptor, known as the peroxisome proliferator-activated receptor (PPAR), and its endogenous ligand(s) also remain unknown. Peroxisome proliferators inhibit mitochondrial beta-oxidation, and one hypothesis is that the dicarboxylic fatty acid metabolites of accumulated LCFA, formed via the P-450 4A1 omega-oxidation pathway, serve as primary inducers of L-FABP and peroxisomal beta-oxidation. We have tested this hypothesis in primary hepatocyte cultures exposed to clofibrate (CF). Inhibition of P-450 4A1 markedly diminished, via a pre-translational mechanism, the CF induction of L-FABP and peroxisomal beta-oxidation. In further experiments, long-chain dicarboxylic acids, the final products of the P-450 4A1 omega-oxidation pathway, but not LCFA, induced L-FABP and peroxisomal beta-oxidation pre-translationally. These results suggest a role, in part, for long-chain dicarboxylic acids in mediating the peroxisome proliferator induction of L-FABP and peroxisomal beta-oxidation. We also found that LCFA, which undergo rapid hepatocellular metabolism, could become inducers of L-FABP and peroxisomal beta-oxidation under conditions where their metabolism was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Determinants of protein modification versus heme alkylation: inactivation of cytochrome P450 1A1 by 1-ethynylpyrene and phenylacetylene.

Reaction of cytochrome P450 enzymes with arylacetylenes results in heme N-alkylation [e.g., Komives, E. A., and Ortiz de Montellano, P. R., (1985) J. Biol. Chem. 260, 3330-3336] and/or protein modification [e.g., Gan, L.-S. L., Acebo, A. L. and Alworth, W. L. (1984) Biochemistry 23, 3827-3836]. To clarify the factors that determine whether heme or protein alkylation occurs, we have investigated the cytochrome P450 1A1-catalyzed oxidation of 1-ethynylpyrene (1-EP) and phenylacetylene (PA). Cytochrome P450 1A1 in microsomes from beta-naphthoflavone-induced rats is inactivated in a time- and NADPH-dependent manner by 1-EP and PA. Parallel loss of the heme chromophore is observed with PA but not with 1-EP, although partial heme chromophore loss is observed when the purified, reconstituted enzyme is inactivated by either agent. Product analysis shows that 1-EP and PA are oxidized to, respectively, (1'-pyrenyl)-acetic and phenylacetic acids. In contrast to the inactivation of cytochrome P450 2B1 by PA, no isotope effect is observed on enzyme inactivation or metabolite formation when the acetylenic hydrogen is replaced by deuterium in either 1-EP or PA. Inactivation of cytochrome P450 1A1 by 1-EP results in covalent binding of 0.8-0.9 equiv (relative to total cytochrome P450 content) of the inhibitor to the microsomal protein. The results demonstrate that a single isozyme can be inactivated, depending on the structure of the arylacetylene, by heme or protein alkylation. Spectroscopic binding constants (Ks) show that 1-EP binds to the enzyme with > 2000 times greater affinity that PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylene↗
PubMedDate not supplied

A case of episcleral neurofibroma.

PURPOSE: To report a rare case of episcleral neurofibroma and discuss the possible differential diagnoses. METHODS: Case report of a 36-year-old man who presented with a painless epibulbar mass of the left eye. We describe the clinical and histopathologic features of the tumour and compare it with other tumours which may have a similar clinical presentation. RESULTS: An excisional biopsy of the tumour was performed. Histopathologic examination revealed the tumour to be an isolated episcleral neurofibroma. CONCLUSION: It is often difficult to clinically differentiate this tumour from other conditions. Because of the slow growth of neurofibromas and its slow risk of malignant transformation, these lesions may be observed periodically for progression. Surgical excision may be performed if the lesion is found to be progressively enlarging in size.

Adult↗
PubMedDate not supplied

A numerical investigation on the steady and pulsatile flow characteristics in axi-symmetric abdominal aortic aneurysm models with some experimental evaluation.

Steady and pulsatile flow characteristics in rigid abdominal aortic aneurysm (AAA) models were investigated computationally (using Fluent v. 4.3) over a range of Reynolds number (from 200 to 1600) and Womersley number (from 17 to 22). Some comparisons with measurements obtained by particle image velocimetry under the pulsatile flow conditions are also included. A sinusoidal inlet flow waveform 1 + sin omega t with thin inlet boundary layers was used to produce the required pulsatile flow conditions. The bulk features of the mean flow as well as some detailed features, such as wall shear stress distributions, are the foci of the present investigation. Recirculating vortices appeared at different phases of a flow cycle causing significant spatial and temporal variations in wall shear stresses and static pressure distributions. A high level of shear stresses usually appeared at the upstream and downstream ends of the bulge. Effects of pressure rise caused by the increase in cross-sectional area were transmitted into the downstream tube. Further simulation studies were conducted using simulated physiological waveforms under resting and exercise conditions so as to determine the possible implication of vortex dynamics inside the AAA model.

Aortic Aneurysm, Abdominal↗
PubMedDate not supplied

A phase II study of carboplatin in nasopharyngeal carcinoma.

This is a phase II study to evaluate the efficacy and toxicity of short-course carboplatin in advanced-stage nasopharyngeal carcinoma (NPC). Thirty-three previously untreated stage III-IV NPC patients were studied. Carboplatin was given as a rapid intravenous injection every 3 weeks. The dose of carboplatin was calculated according to the individual patient's creatinine clearance and desired platelet nadir of 75,000/microliter according to the Egorin formula. Response and toxicity were evaluated. Thirty-two patients were evaluated for response. The median age was 54 years, range 30-70 years. Twenty-four patients had local regional disease and 8 patients had metastatic disease. The median dose of carboplatin given was 415 mg/m2 (range 91-791 mg/m2). Fourteen (44%) patients had a partial response with a 95% confidence interval of 26-62%. Fifteen (47%) patients had stable disease and 3 (9%) progressive disease. The overall median survival rate was not reached at 43 months. Overall toxicity was tolerable. Grade III-IV myelosuppression occurred in 4 (12%) patients. There were no other major toxicity- or treatment-related deaths. We conclude that carboplatin has a significant anticancer effect in advanced NPC. Thus carboplatin combination chemotherapy for the treatment of NPC is worthy of future clinical investigations.

Adult↗
PubMedDate not supplied

Photorefractive keratectomy for myopia of 6 to 12 diopters.

To conduct a prospective, nonrandomized clinical trial to assess the efficacy, stability and safety of the use of excimer laser photorefractive keratectomy (PRK) to correct myopia of greater than -6.00 diopters (D) in Singapore. Two hundred thirty-three eyes of 176 patients with a mean preoperative spherical equivalent refraction of -8.70 +/- 2.3 D (range, -5.75 D to -18.13 D) underwent PRK with a 193nm ArF excimer laser (ExciMed, Summit) for myopic corrections of between -6.20 D and -11.90 D. The first 66 of 233 eyes that reached at least 1 year of postoperative follow up are reported. One year postoperatively, the mean manifest spherical equivalent refraction was -1.50 D +/- 1.90 D (range -6.25 D to +3.25 D); 34% of eyes were within +/- 1.00 D of attempted correction; uncorrected visual acuity was 20/40 or better in 75% of eyes. No eyes lost two or more Snellen lines of spectacle corrected visual acuity. Central corneal haze was mild in 20% of eyes and moderate in 3% of eyes. Five eyes developed ocular hypertension that subsequently resolved with treatment. Excimer laser PRK is reasonably effective and safe in the treatment of -6.00 D to -12.00 D of myopia. However, it is less accurate than PRK in eyes with low to moderate myopia and is more likely to result in significant corneal haze.

Adult↗
PubMedDate not supplied

Autologous keratophakia for the correction of consecutive hyperopia after automated lamellar keratoplasty for myopia.

PURPOSE: Consecutive hyperopia occurs if too much corneal tissue is resected during automated lamellar keratoplasty for myopia. We report what are, to our knowledge, the first two cases of consecutive hyperopia after automated lamellar keratoplasty that were treated by keratophakia with autologous corneal tissue. METHODS: The patient in case 1 had a spherical equivalent refraction of +3.38 diopters (D) and the patient in case 2 a refraction of +3.63 D in each eye after automated lamellar keratoplasty for myopia. Corneal tissue from the contralateral eye of each patient was obtained with an automated microkeratome and transferred to the overcorrected eye in an autologous keratophakia procedure. RESULTS: The patient in case 1 had an unaided visual acuity of 20/20, with a spherical equivalent refraction of +0.63 D 4 months after the autologous keratophakia. The patient in case 2 had an unaided visual acuity of 20/60, with a spherical equivalent refraction of -2.25 D 2.5 months postoperatively. CONCLUSION: These two cases illustrate the use of simultaneous contralateral myopic automated lamellar keratoplasty with autologous keratophakia to treat eyes overcorrected following previous automated lamellar keratoplasty for myopia.

Adult↗