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Biomedical subjects

J K Chen

Publications and source records attributed to J K Chen.

At least 145 records · Page 8Linked to original sources
PubMed1986

Role of lipoproteins in growth of human adult arterial endothelial and smooth muscle cells in low lipoprotein-deficient serum.

Recently improved culture conditions for human adult arterial endothelial and smooth muscle cells from a wide variety of donors have been used to study the effects of lipoproteins on proliferation of both cell types in low serum culture medium. Optimal growth of endothelial and smooth muscle cells in an optimal nutrient medium (MCDB 107) containing epidermal growth factor, a partially purified fraction from bovine brain, and 1% (v/v) lipoprotein-deficient serum was dependent on either high- or low-density lipoprotein. High- and low-density lipoprotein stimulated cell growth by three- and five-fold, respectively, over a 6-day period. Optimal stimulation of both endothelial and smooth muscle cell growth occurred between 20 and 60 micrograms/ml of high- and low-density lipoproteins, respectively. No correlation between the activation of 3-hydroxyl-3-methylglutaryl coenzyme. A reductase activity and lipoprotein-stimulated cell proliferation was observed. Lipid-free total apolipoproteins or apolipoprotein C peptides from high-density lipoprotein were partially effective and together with oleic acid effectively replaced native high-density lipoprotein for the support of endothelial cell growth. In contrast, apolipoproteins or apolipoprotein C peptides from high-density lipoprotein alone or with oleic acid had no effect on smooth muscle cell proliferation. The results suggest a functional role of high- and low-density lipoproteins and apolipoproteins in the proliferation of human adult endothelial and smooth muscle cells.

Apolipoproteins↗
PubMed1986

A pharmacokinetic and pharmacodynamic study of a 'visiting pill' containing norethisterone.

The pharmacokinetics and pharmacodynamic effects of two doses of norethisterone (5mg and 3mg) used as a 'visiting pill' were investigated. There were no significant differences in the pharmacokinetics of the two doses except for the peak concentration achieved and the bioavailability as assessed by the area under the serum norethisterone concentration - time curve. Both doses were rapidly absorbed. Pharmacodynamic effects were minor. No change occurred in serum concentrations of total cholesterol, total triglycerides or HDL-cholesterol. The area under the serum glucose concentration--time curve and particularly the area under the serum insulin concentration--time curve were significantly increased as a result of treatment but no change occurred in the serum levels of glycosylated haemoglobin. SHBG concentrations in serum decreased on treatment whereas those of ceruloplasmin increased.

Absorption↗
PubMed1986

Biochemical characterization of the cholesterol-dependent growth of the NS-1 mouse myeloma cell line.

The biochemical basis for the cholesterol-dependent growth phenotype of the NS-1 myeloma cell line has been investigated. In one series of experiments, the growth response of NS-1 cells to several of the intermediates of cholesterol biosynthesis was studied in serum-free medium. The cholesterol precursors, squalene and lanosterol, were totally ineffective in promoting NS-1 cell growth. In contrast, cholesterol precursors downstream from lanosterol, i.e., desmosterol and 7-dehydrocholesterol, completely replaced cholesterol in supporting NS-1 cell growth. In a second series of experiments, NS-1 cells and NS-1-503 cells (a cholesterol growth-independent variant of NS-1 cells) were labelled with [2-14C]acetate and the distributions of radioactivity between cholesterol and its precursors were determined by thin-layer chromatography using two different solvent systems. The major labelled sterol product (greater than 80%) in NS-1 cells after a 24-h exposure to [2-14C]acetate was lanosterol. In contrast, the major labelled sterol product (greater than 95%) in NS-1-503 cells after a 24-h exposure to [2-14C]acetate was cholesterol. Taken together, these results indicate that NS-1 cells are defective in cholesterol biosynthesis and identify the site of lesion as the demethylation of lanosterol to C-29 sterol intermediates.

Acetates↗
PubMed1986

The observation of some biological characteristics of transformed cells induced by MNNG in vitro.

The early passage diploid Syrian hamster embryo (SHE) cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The treated cells proliferated rapidly; the doubling times shortened; colonies appeared in solid agar medium and transformed foci formed in tissue culture. All of these phenomena suggest that malignant transformation of SHE cell has occurred. Faster cell division rate and multipolar mitosis were demonstrated by time-lapse cinemicrography and scanning electron microscopy. Multipolar mitosis can occur in two forms: direct division and indirect division. The transformed cells were more abundant in microvilli, the number of which increased in accordance with the degree of malignancy. In comparison with the controls, the transformed cells expressed a greater tritiated thymidine incorporation, greater DNA contents and more chromosomes, but no difference in nuclear area. The determination of amino acid changes in media due to the growth of transformed cells showed that the decrease in arginine and increase in ornithine are significant. The results of allogenic animal inoculation suggest that the transformed cells can be characterized into several different stages in the process of transformation.

Animals↗
PubMed1986

Antimycobacterial activities of two newer ansamycins, R-76-1 and DL 473.

The antimycobacterial activities of two newer ansamycins, isobutylpiperazinylrifamycin SV (R-76-1) and cyclopentylrifamycin SV (DL 473), were compared with those of rifampin (RMP) both in vitro and in vivo. In terms of minimal inhibitory concentrations against a number of cultivable mycobacteria, R-76-1 was about eight times more active in vitro than RMP; whereas DL 473 was only slightly more active than RMP. Therapeutic activities of R-76-1 versus RMP and DL 473 versus RMP were compared, respectively, in the experimental infection of mice with Mycobacterium lepraemurium by different treatment schedules (immediate and delayed) and dosage regimens. R-76-1 appeared to have been three times more effective than RMP; DL 473 was also more effective than RMP in that an equivalent therapeutic effect could be obtained by fewer doses of DL 473 than of RMP, and in that DL 473 exerted a more prolonged activity than RMP. With the kinetic method and a dosage of 0.001% in the diet, R-76-1 demonstrated a bactericidal-type effect against M. leprae whereas RMP did not; with the proportional bactericidal method, R-76-1 possessed about three times the bactericidal activity of RMP against M. leprae. When drugs were administered once in 4 weeks, the RMP dose required to prevent multiplication of M. leprae in the foot pads of half of the mice was in the range of 1.25 to 2.5 mg/kg; whereas that of DL 473 was less than 0.625 mg/kg. With the proportional bactericidal method, even a single dose of 1.25 mg DL 473 per kg was active against M. leprae; whereas the smallest single active dose of RMP was 10 mg/kg. DL 473 in single doses of 5 mg/kg and 10 mg/kg was significantly more effective than RMP in equal doses and, among the intermittent regimens administered four times, once every 4 weeks, no significant differences of bactericidal activity were observed between RMP at 20 mg/kg and DL 473 at 0.625 mg/kg. A preliminary clinical trial of R-76-1 in 20 patients with lepromatous leprosy showed that the compound, administered in a dosage of 150 mg daily, was very effective.

Animals↗
PubMed1985

Photochemical cross-linking of tRNA1Arg to the 30S ribosomal subunit using aryl azide reagents attached to the anticodon loop.

The 2-thiocytidine residue at position 32 of tRNA1Arg from Escherichia coli was modified specifically with three photoaffinity reagents of different lengths, and the corresponding N-acetylarginyl-tRNA1Arg derivatives were cross-linked to the P site of E. coli 70S ribosomes by irradiation. Covalent attachment was dependent upon the presence of a polynucleotide template and exposure to light of the appropriate wavelength. From 4% to 6% of the noncovalently bound tRNA became cross-linked to the ribosome as a result of photolysis, and attachment to the P site was confirmed by the reactivity of arginine in the covalent complexes toward puromycin. Analysis of the irradiated ribosomes by sucrose-gradient sedimentation at low Mg2+ concentration revealed that the tRNA was associated exclusively with the 30S subunit in all cases. Two of the N-acetylarginyl-tRNA1Arg derivatives were attached primarily to ribosomal proteins whereas the third was cross-linked mainly to 16S RNA. Partial RNase digestion of the latter complex demonstrated that the tRNA had become attached to the 3' third of the rRNA molecule. In addition, the tRNA-rRNA bond was shown to be susceptible to cleavage by hydroxylamine and mercaptoethanol.

Anticodon↗
PubMed1985

Covalent cross-linking of tRNAGly1 to the ribosomal P site via the dihydrouridine loop.

The dihydrouracil residue at position 20 of Escherichia coli tRNAGly1 has been replaced by the photoaffinity reagent, N-(4-azido-2-nitrophenyl)glycyl hydrazide (AGH). The location of the substituent was confirmed by the susceptibility of the modified tRNA to cleavage with aniline. When N-acetylglycyl-tRNAGly1 derivatized with AGH was bound noncovalently to the P site of E. coli 70 S ribosomes, 5-6% on average was photochemically cross-linked to the ribosomal particles in a reaction requiring poly(G,U), irradiation and the presence of the AGH label in the tRNA. Approximately two-thirds of the covalently attached tRNA was associated with 16 S RNA in the 30 S subunit. This material was judged to be in the P site by the criterion of puromycin reactivity. As partial RNAase digestion of the tRNA-16 S RNA complex produced labeled fragments from both 5' and 3' segments of the rRNA, there appeared to be more than one site of cross-linking in the 30 S subunit. The small amount of N-acetylglycyl-tRNAGly1 associated with the 50 S subunit was also linked mainly to rRNA, but it was not puromycin-reactive.

Affinity Labels↗
PubMed1983

Preoperative cervical dilatation by vaginal pessaries containing prostaglandin E1 analogue.

A double-blind trial comparing use of placebo with use of a single intravaginal pessary of 1 mg 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester, inserted approximately three hours before first-trimester surgical abortion, was carried out. There were 54 women each in the study and control groups. A spring gauge was used to record the force required to dilate the cervix. With the use of the prostaglandin analogue, operative time, blood loss, and the need for additional mechanical dilatation of the cervix were significantly reduced compared with the control group (P less than .0001). This reduction greatly facilitates the operation and should reduce the incidence of cervical trauma.

Abortifacient Agents↗