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Biomedical subjects

E W Gabrielson

Publications and source records attributed to E W Gabrielson.

26 records · Page 2Linked to original sources
PubMed1988

Role of oxygen radicals in 12-O-tetradecanoylphorbol-13-acetate-induced squamous differentiation of cultured normal human bronchial epithelial cells.

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits growth and induces terminal squamous differentiation of normal human bronchial cells when added to the culture media [J. C. Willey, A. J. Saladino, C. Ozanne, J. F. Lechner, and C. C. Harris, Carcinogenesis (lond.), 5: 209-215, 1984]. We have investigated the possibility of oxygen free radicals being involved as intermediates in this process. Electron paramagnetic resonance measurements using the spin-trapping agent 5,5-dimethyl-1-pyrroline-1-oxide failed to detect oxygen free radicals in bronchial epithelial cells exposed to TPA, although oxy radicals were detected in bronchial epithelial cells after a nontoxic exposure to menadione, and in human neutrophils after exposure to TPA. Addition to the culture media of free radical scavenger, i.e., reduced glutathione, N-acetylcysteine, D-alpha-tocopherol, copper (II) (3,5-diisopropylsalicyclic acid)2, or the combination of superoxide dismutase and catalase did not affect the dose-dependent growth inhibition of TPA on the bronchial epithelial cells. Moreover, exposure of the bronchial epithelial cells to TPA did not result in increased DNA single strand breaks measured by alkaline elution, as would be expected with a free radical mediated mechanism. Thus, our results argue against the importance of oxygen free radicals in the inhibition of growth and the induction of squamous differentiation by TPA in normal human bronchial epithelial cells.

Acetylcysteine↗
PubMed1988

Stimulation of DNA synthesis in cultured primary human mesothelial cells by specific growth factors.

Monolayer cultures of human mesothelial cells made quiescent by serum deprivation are induced to undergo one round of DNA synthesis by platelet-derived growth factor (PDGF), epidermal growth factor (EGF), or transforming growth factor type beta 1 (TGF-beta 1). This one-time stimulation is independent of other serum components. The kinetics for induction of DNA synthesis observed for PDGF, EGF, and TGF-beta 1 are all similar to one another, with a peak of DNA synthesis occurring 24-36 h after the addition of the growth factors. Repetitive rounds of DNA synthesis and cell division do not ensue after addition of PDGF, EGF, or TGF-beta 1 alone or in combination; however, in media supplemented with chemically denatured serum, each of these factors is capable of sustaining continuous replication of mesothelial cells. Stimulation of growth by PDGF and TGF-beta 1 is unusual for an epithelial cell type, and indicates that mesothelial cells have growth regulatory properties similar to connective tissue cells.

Cells, Cultured↗
PubMed1987

Comparison of production of transforming growth factor-beta and platelet-derived growth factor by normal human mesothelial cells and mesothelioma cell lines.

Steady state mRNA levels for transforming growth factor beta, platelet-derived growth factor (PDGF) A-chain, and PDGF B-chain were measured in normal human mesothelial cells, SV40 large T-antigen expressing human mesothelial cells, and human mesothelioma cell lines. The mRNA expression level for transforming growth factor beta was similar in all three types of culture while normal human mesothelial cells secrete more transforming growth factor beta than do mesothelioma cell lines or T-antigen expressing mesothelial cells. In contrast, both PDGF A- and B-chain mRNAs are expressed at higher levels in mesothelioma cell lines than in normal human mesothelial cells. PDGF-like mitogenic activity was readily detectable in medium conditioned by a mesothelioma cell line and was undetectable in conditioned medium from normal cells. These results suggest the hypothesis that PDGF may be an autocrine growth factor in mesothelioma.

Cell Line↗
PubMed1987

Diffusion of singlet oxygen into human bronchial epithelial cells.

The respiratory epithelium undergoes morphological and functional changes following exposure to single oxygen. However, mechanisms by which singlet oxygen causes cellular injury are unclear. The present experiments were designed to investigate the possibility that singlet oxygen, a highly reactive species, diffuses into respiratory epithelial cells. Of the various methods for detection of singlet oxygen, the electron spin resonance (ESR) spectrometric technique was judged to be most compatible and sensitive for use with cell suspensions. ESR spectrometry was used to monitor the singlet oxygen-mediated conversion of 2-(9,10-dimethoxyanthracenyl)-tert-butylhydroxylamine, (I), to 2-(9,10-dimethoxyanthracenyl)-tert-butylnitroxide, (II), and its corresponding endoperoxide, (III), in human bronchial epithelial cells treated with extracellularly generated singlet oxygen. In a second series of experiments, bronchial epithelial cells labeled with (I) were treated with singlet oxygen in the presence of 1,4-diazabicyclo[2.2.2]octane, a singlet oxygen quenching agent. The addition of this quenching agent eliminated the ESR spectrum corresponding with (II) and (III). This result is consistent with the quenching of singlet oxygen by 1.4-diazabicyclo[2.2.2]octane. Collectively, our results indicate that extracellularly generated singlet oxygen diffuses into human bronchial epithelial cells and that this process is a potentially important step in the cytotoxic action of singlet oxygen to the respiratory epithelium.

Anthracenes↗
PubMed1986

Studies on the role of oxygen radicals in asbestos-induced cytopathology of cultured human lung mesothelial cells.

The possible role of oxygen radicals in mediating the cytopathologic effects of asbestos was studied using human mesothelial cells in culture. Electron paramagnetic resonance measurements of intact cells using the spin trap 5,5-dimethyl-1-pyrroline-1-oxide failed to detect any increase in oxygen radicals in mesothelial cells after exposure to amosite asbestos, although oxygen radicals were readily detected in cells exposed to menadione, an uncoupler of oxidation-reduction reactions. Cellular thiol levels were reduced after exposure to menadione, but were not affected by exposure to asbestos. Addition to the culture media of the free radical scavengers superoxide dismutase, reduced glutathione, N-acetylcysteine, or D-alpha-tocopherol had no affect on the dose-dependent cytotoxicity of amosite fibers. Furthermore, exposure of the mesothelial cells to amosite fibers resulted in no significant increase in the level of DNA single-strand breaks. These results all suggest that for cultured human mesothelial cells, oxygen free radicals are not important mediators of the cytopathic effect of asbestos.

Asbestos↗
PubMed1985

Transformation of human bronchial epithelial cells transfected by Harvey ras oncogene.

Transfection of normal human bronchial epithelial (NHBE) cells with a plasmid carrying the ras oncogene of Harvey murine sarcoma virus (v-Ha ras) changed the growth requirements, terminal differentiation, and tumorigenicity of the recipient cells. One of the cell lines isolated after transfection (TBE-1) was studied extensively and shown to contain v-Ha ras DNA. Total cellular RNA from TBE-1 cells hybridized to v-Ha ras structural gene fragment probes five to eight times more than RNA from parental NHBE cells. The TBE-1 cells expressed phosphorylated v-Ha ras polypeptide p21, showed a reduced requirement for growth-factor supplements, and became aneuploid as an early cellular response to v-Ha ras expression. As the transfectants acquire an indefinite life-span and anchorage independence they became transplantable tumor cells and showed many phenotypic changes suggesting a pleiotropic mechanism for the role of Ha ras in human carcinogenesis.

Animals↗
PubMed1975

Electrical modification of disuse osteoporosis.

Localized electrical stimulation of the immobilized hind limb of young rabbits resulted in dramatically more bone in the tuber calcis (heel bone) compared to the severe loss of bone (osteoporosis) seen in unstimulated, immobilized controls. Detailed histological evaluation using microradiography and fluorescence and polarization microscopy showed that the increase was probably due to an overall inhibition of surface cortical bone loss )endosteal resorption) and an increase in the quantity of the new immature bone. There was also evidence of increased osteonal resorption in the stimulated animals.

Animals↗