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Biomedical subjects

K Y Chan

Publications and source records attributed to K Y Chan.

6 recordsLinked to original sources

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 The addition of 1 mM dibutyryl cyclic AMP to the neuroblastoma cells, at the time when the serum was withdrawn, enhanced the rate of differentiation and the redistribution of tubulin and tubulin-like proteins within the 3 cellular compartments.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

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

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

Identification of basic metabolites of 4-[4-(p-chlo- robenzoyl)piperidino]-4'-fluorobutyrophenone, an experimental neuroleptic agent.

Two metabolites of 4-[4-(p-(chlorobenzoyl)piperidino]-4'-fluorobutyrophenone (RMI 9901) as well as unchanged drug, have been identified in the urine of rats following oral administration of the drug. Analysis of basic urine extracts by combined gas chromatography-mass spectrometry was employed for metabolite identification. N-dealkylation appears to be a major metabolic pathway and results in formation of 4-(p-chlorobenzoyl)piperidine (I). Subsequent oxidation of this metabolite results in the formation of 4-(p-chlorobenzoyl)-2-piperidone (II), and represents rather unusual metabolic pathway for compounds of this chemical class.

Animals

Decrease in the activity of the drug-metabolizing enzymes of rat liver following the administration of tilorone hydrochloride.

Tilorone hydrochloride, 2,7-bias(2-(diethylamino)ethoxy(fluoren-9-one dihydrochloride, has been studied to determine its effect on the drug-metabolizing enzymes of the liver of male Charles River CD strain rats. Single and multiple doses of tilorone-HCl, 100 mg/kg/day po, were used. Most experiments were performed 24 hr after the last dose, except for a study 5 hr after dosing, and those in which the duration of effects of tilorone hydrochloride were determined. The hexobarbital sleeping time was prolonged after both single doses and four doses of tilorone hydrochloride. The 4-dose regimen prolonged the zoxazolamine paralysis time but the single dose did not. A decrease in microsomal protein was observed after the single- and 4-dose regimens but not after 21 daily doses of tilorone-HCl. Cytochrome P-450 content of microsomes was decreased by the single doses, 100 and 250 mg/kg po, and by 4 and 21 doses of 100 mg/kg/day po. Activities of aminopyrine demethylase and hexobarbital oxidase also were decreased by the above regimens, but the activity of hexobarbital oxidase was affected more markedly. Electron micrographs of rat liver, after treatment with tilorone-HCl, 100 mg/kg/day for 21 days, revealed many membranous structures in the form of whorls.

Aminopyrine N-Demethylase