Biomedical subjects

K Y Chan

Publications and source records attributed to K Y Chan.

At least 145 records · Page 8Linked to original sources

PubMed1981

Phenytoin and phenobarbitone plasma level-dose relationships in Chinese epileptic children in Singapore.

In a study of 30 Chinese epileptic children, 43% had poor seizure control. The average daily dose of phenytoin was 6.1 +/- 0.53 mg/kg, and the mean plasma level was 4.2 +/- 0.63 microgram/ml, as determined by the enzyme immunoassay (EMIT) method. The phenytoin plasma level (microgram/ml) versus daily dose (mg/kg) ratios in 73% of these patients were below 1. The average daily dose of phenobarbitone was 5.1 +/- 0.36 mg/kg, and the mean plasma level was 24.8 +/- 1.7 microgram/ml -- also estimated by EMIT. Only one patient showed adverse effects. Poor seizure control in patients was chiefly due to subtherapeutic concentrations of phenytoin, which cannot be attributed to poor patient compliance. The presence of phenobarbitone might have accelerated phenytoin metabolism, or the drug could have been lost through sweating. The pharmacokinetics of phenytoin in these Chinese children may be genetically different and might have caused the subtherapeutic phenytoin levels.

Adolescent↗

PubMed1981

Differential uptake of horseradish peroxidase isoenzymes by cultured neuroblastoma cells.

The endocytotic uptake and intracellular decay of horseradish peroxidase isoenzymes C and A by cultured mouse neuroblastoma cells were analyzed quantitatively by a direct spectrophotometric assay. At concentrations below 1 mg/ml, the rate of uptake of the isoenzyme C was more than three times as much as the isoenzyme A. This differential uptake suggests that previous claims of horseradish peroxidase being endocytosed only in the nonselective fluid phase are oversimplified. The implication of this selectivity in the biological significance of retrograde axonal transport of proteins by neuronal systems is discussed.

Animals↗

PubMed1981

Action of a trophic factor(s) from rabbit corneal epithelial culture on dissociated trigeminal neurons.

Cultured corneal epithelial cells release a factor(s) that stimulates trigeminal neurons to form neurites in vitro. To characterize this trophic effect, conditioned media (serum free, supplemented) from cultures for corneal epithelium, stromal fibroblasts, and endothelium were studied further. Only epithelial conditioned medium (PCM) prolonged neuronal survival and induced neurite outgrowth. This trophic influence peaked after 2 to 3 days and gradually declined thereafter during a week when the medium was not renewed. Using a bioassay to score the percentage of initially viable neurons that extended neurites, it was found that the trophic effect of PCM was proportional to the conditioned medium concentration and to the cell density of the epithelial culture used for the conditioning. Maximum activity in PCM was correlated with confluency of the epithelial culture. Experiments using antiserum to nerve growth factor (NGF) and purified antibody to cold-insoluble globulin (CIG) indicated that the tropic effect of PCM was not derived from NGF or CIG. The trophic activity of PCM was abolished totally by heat or trypsin treatment but was not affected by collagenase. Although a fraction of the trophic activity was associated with the substratum after adsorption of PCM, this and other evidence did not suggest that the primary action of PCM was to enhance neuronal adhesion.

Animals↗

PubMed1980

Endocytosis and compartmentation of peroxidases and cationized ferritin in neuroblastoma cells.

To investigate further the selectivity of retrograde axonal transport of horseradish peroxidase (HRP) isoenzymes previously observed in the rat central visual pathways, cultured mouse neuroblastoma cells (clone N18) were examined for selectivity of endocytosis of peroxidases and cationized ferritin in vitro. Differentiating N18 cells were incubated with proteins in various timing and pulse-chase experiments, and examined for the ultrastructural localization of endocytosed protein using cytochemical techniques. Semi-quantitative morphometry was performed on some of the samples. Major findings were as follows. (1) The protein was internalized into vesicles (coated and uncoated), short tubules and occasional small cup-shaped bodies within the first few minutes, and transferred via tubules and uncoated vesicles to secondary lysosome-like organelles (vacuoles, multivesicular bodies and dense bodies) from 5 to 15 min, with dense bodies representing the final site of protein accumulation. All the proteins tested were endocytosed through the same pathways in the soma and neurite of the cell. (2) There was no indication of a net orthograde or retrograde neuritic transport proteins. (3) There were induced increases in both vesicle and tubule formation as a result of protein endocytosis, with HRP isoenzyme C showing the greatest effect. (4) The apparent rate of internalization of HRP isoenzyme C into vesicles during the initial 5 min was significantly greater than for other peroxidases amd cationized ferritim. (5) Relatively more tubules than vesicles were involved in the uptake of protein as endocytosis was prolonged from 5 min to 8 h, with HRP isoenzyme C showing the largest effect. (6) There were indications of preferential compartmentation of endocytosed protein into certain organelles.

Animals↗

PubMed1979

Compartments of tubulin and tubulin-like proteins in differentiating neubroblastoma cells.

Cytoplasmic, tubular and particulate fractions of differentiating neuroblastoma cells were prepared and the tubulin together with tubulin-like proteins was measured in each cell fraction during different stages of cell differentiation. In undifferentiated cells, 73%, 5% and 22% of the tubulin and tubulin-like proteins were contained in the cytoplasmic, tubular and particulate fractions, respectively. After 5 days of differentiation, the overall content of tubulin and tubulin-like proteins had increased by 73%. This corresponded to increases of 45%, 145% and 100% in the cytoplasmic, microtubular and particulate fractions, respectively. The increase in membrane-bound (particulate) tubulin and tubulin-like proteins was significantly greater than the total increase of proteins in the particulate fraction. Polyacrylamide gel electrophoresis of the proteins in each subcellular fraction revealed the presence of protein bands corresponding to the alpha and beta subunits of tubulin. Whereas these bands indicated equal amounts of protein in the alpha and beta positions for the tubular and particulate cell fractions, an analysis of the cytoplasmic fraction revealed much more protein migrating to the alpha-tubulin position than to the beta-tubulin position, especially during cell differentiation. Furthermore, two overlapping but distinct protein bands were demonstrable in the position of the alpha-tubulin from the cytoplasmic fraction. These bands were designated alpha 1 and alpha 2. The particulate fraction contained only the alpha 1 and the tubular fraction only the alpha 2 protein band. The addition of 1 mM dibutyryl cyclic AMP to the neuroblastoma cells, at the time when the serum was withdrawn, enhanced the rate of differentiation and the redistribution of tubulin and tubulin-like proteins within the 3 cellular compartments. These results are discussed as they relate to the regulation, biosynthesis, turnover and compartmentation of tubulin and tubulin-like proteins in differentiating neuroblastoma cells.

Animals↗

PubMed1978

An association between mitochondria and microtubules in synaptosomes and axon terminals of cerebral cortex.

A substantial number of synaptosomes prepared from rat cerebral cortex were found by electron microscopy to contain a horseshoe-shaped mitochondrion flanked by an arc of three to ten microtubules opposite the synaptic membrane specializations. The microtubules were replaced by characteristic paracrystals following the incubation of synaptosomes with vinblastine sulfate. A similar spatial organization of microtubules and mitochondria was also observed in some axon terminals of the cerebral cortex in situ. The significance of this novel observation is discussed with regard to the role of microtubules in axonal transport at the synaptic terminal and previous reports on the identification of tubulin in synaptosomes and subsynaptic structures.

Animals↗

PubMed1977

Plasma arginine esterase activity in cystic fibrosis of the pancreas.

Using a micro-method for the determination of plasma arginine esterase activity, we have investigated the values for soybean trypsin inhibitor (STI)-inhibited arginine esterase activity in patients with cystic fibrosis, obligate heterozygotes and age matched control individuals. The mean of STI-inhibited activity is lowest for cystic fibrosis patients while the mean for normal controls is the highest. The mean of STI-inhibited activity for the heterozygotes is midway between the values of the patients and the normal individuals. The deficiency of arginine esterase activity was statistically significant for both cystic fibrosis patients and heterozygotes.

Adolescent↗

PubMed1976