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Biomedical subjects

G Z Chen

Publications and source records attributed to G Z Chen.

At least 37 records · Page 2Linked to original sources
PubMed1989

Capillary cloning of primary human tumor cells: assay miniaturization for drug efficacy testing.

The conventional double-layer agar method of cloning human tumor cells requires a substantial number of viable tumor cells and 14-21 days of culture. These prerequisites frequently limit its utility as an assay. In an attempt to circumvent these limitations and to reduce the amount of drug that is needed in the assay, we have further developed and miniaturized the assay in which human tumor cells are cloned in glass microcapillary tubes. Cultures consisted of 50 microliters containing 15,000 nucleated cells in 975 mm capillary tubes which were incubated for seven days. The results from 50 consecutive tumor biopsies resulted in cloning efficiencies, ranging from 0.007% to 1.0% with an overall successful cloning of 88% of all tumors tested and a good linear growth relationship and chemotherapy sensitivity. This miniaturized assay offers distinct advantages for drug efficacy testing including high cloning efficiencies, small tumor sample and drug requirements, quicker assay turnaround time and a general conservancy of reagents and incubator space.

Antineoplastic Agents↗
PubMed1989

Glutamine- vs glucose-supported motor activity in Schistosoma mansoni: physiological relevance of aerobic metabolism.

The ability of Schistosoma mansoni to generate energy through aerobic metabolic processes was examined in adult parasites in vitro. Parasite catabolism of radiolabeled glucose, glutamine, and other amino acids to CO2 and Krebs cycle intermediates was measured under a variety of incubation conditions. L-Glutamine was metabolized to CO2 via the intermediates glutamate, alpha-ketoglutaramate, and alpha-ketoglutarate in worms incubated in a balanced salts solution containing this amino acid as the only organic constituent. Of the other amino acids tested, CO2 production was detected from L-glutamate and L-asparagine. The catabolism of L-glutamine to CO2 was reduced by the respiratory inhibitor antimycin A. The motility of schistosomes in culture was maintained for at least 24 hr when L-glutamine was the only carbon source available to the worms. Under these conditions, motility was reduced when parasites were exposed to a respiratory inhibitor such as KCN, antimycin A, rotenone, or oligomycin, but it was completely restored by the addition of glucose to the medium. These results suggest that while the schistosome is capable of limited aerobic energy-generating processes under certain conditions, survival is not contingent upon these processes in the presence of glucose.

Adenine Nucleotides↗
PubMed1989

Physiological role of HMG-CoA reductase in regulating egg production by Schistosoma mansoni.

Pathological lesions observed in humans infected with Schistosoma mansoni are due to the eggs produced by the female parasite. Mevinolin, a potent inhibitor of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) reductase, blocks egg production by this parasite. In this report, we demonstrate that cholesterol precursors, mevalonate and farnesol, stimulate egg production by the female parasite and that these precursors can reverse the mevinolin-induced inhibition of egg production. Because the parasite cannot synthesize cholesterol, we incubated parasites in a culture media containing radiolabeled acetate with and without mevinolin. We isolated nonsterol lipids from the parasite and observed that mevinolin dramatically reduced the conversion of acetate into the polyisoprenoid (dolichols) lipids of the parasite. Dolichols and other nonsterol lipids did not stimulate egg production. HMG-CoA reductase activity was observed in homogenates of the parasite and was inhibited by mevinolin (Ki = 52 nM), but its activity was tripled when the parasite was chronically exposed to low doses of the drug. Parasites with increased reductase activity produced five to six times more eggs. Lastly, chronic administration of large doses of mevinolin to infected mice resulted in a marked reduction of the pathology associated with the infection. These results suggest that egg production in S. mansoni is associated with the parasite's HMG-CoA reductase activity and that a nonsterol lipid produced in the biochemical pathway regulated by this enzyme stimulates egg production.

Animals↗
PubMed1987

Schistosoma mansoni: measurement of Na+ ion activity in the tegument and the extracellular spaces using ion-selective microelectrodes.

Ion-selective microelectrodes were used to measure sodium ion activity (aNa) in the tegument and interstitial spaces in adult male Schistosoma mansoni. In RPMI 1640, aNa averaged 31 +/- 13 mM in the tegument, a value significantly less than that in the bathing medium. In the interstitial spaces, it averaged 72 +/- 17 mM, a value nearly the same as that in the bathing medium. In hypo- or hyperosmotic media, aNa in the interstitial spaces varied by a value commensurate with change in aNa in the medium, but aNa in the tegument was changed by only a small amount. Monensin (10 microM), low temperature (20 C), and ouabain (0.3 to 10 microM) all caused significant increases in aNa in the tegument. Hypo- and hyperosmotic media produced initial weight changes followed by gradual recovery back toward original weights. It is concluded that the schistosome is a volume regulating osmoconformer with osmolality of the extracellular fluid approximating that of the bathing medium, but that within the tegument of the parasite, Na+ concentration is controlled by active transport processes.

Animals↗
PubMed1986

Calmodulin: biochemical, physiological, and morphological effects on Schistosoma mansoni.

Results of radioimmunoassays for the Ca2+-binding protein, calmodulin, revealed that this receptor constitutes 0.53 +/- 0.12% of the total protein in adult male Schistosoma mansoni. Schistosome calmodulin purified by Ca2+-dependent hydrophobic interaction chromatography showed an apparent molecular weight of 19 kDa, and its mobility on sodium dodecyl sulfate polyacrylamide gels was influenced by the presence of Ca2+ but not the antischistosomal drug praziquantel. Calmodulin from the parasite effected a four-fold stimulation of bovine heart adenosine 3',5'-cyclic monophosphate phosphodiesterase; this process was inhibited by removal of Ca2+ with ethyleneglycol-bis(B-aminoethylether)-N,N'-tetraacetic acid but not by praziquantel. Inhibition of calmodulin-activated processes with antipsychotic compounds in vitro resulted in a number of time- and concentration-dependent changes, including inhibition of schistosome calmodulin stimulation of bovine heart phosphodiesterase, disruption and depolarization of the parasite's tegument, and positive inotropic effects on longitudinal musculature. Results of this study indicate that calmodulin is a functional component of schistosomes and suggest that the role it serves is analogous to that obtained in other eukaryotes; i.e., it is an important component of numerous processes regulated, in part, by Ca2+.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Total reconstruction of the ear with auditory function: a two stage procedure.

The rational treatment of severe microtia or anotia should be to restore not only the form but also the auditory function of the ear. To achieve this aim it is obvious that plastic surgeons must co-operate closely with an otologist: yet this degree of co-operation is seldom seen. This paper describes a two-stage procedure for total ear reconstruction with auditory function. In stage I, a tympanoplasty is performed before transplantation of the carved cartilage framework. Stage II consists of elevation of the reconstructed auricle and transplantation of a full-thickness skin graft to the post-auricular defect. Certain modifications of the operative techniques that we have found useful are discussed in detail.

Ear Canal↗
PubMed1984

The free thigh flap: a new free flap concept based on the septocutaneous artery.

Based on the septocutaneous artery flap concept, the thigh, which is the commonest conventional donor site for split-skin grafts, can also become a donor area for skin flaps. The thigh flap, with its large and long neuro-vascular pedicle, can be used either as a free flap or as an island flap as an alternative to the lower abdominal flap, groin flap, tensor fasciae latae myocutaneous flap, sartorius myocutaneous flap or the gracilis myocutaneous flap. The anatomical basis, operative technique and characteristics of the thigh flap are discussed.

Adult↗