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Biomedical subjects

G Arthur

Publications and source records attributed to G Arthur.

63 records · Page 4Linked to original sources
PubMed1980

The presence of lysophosphatidylcholine in chromaffin granules.

Lysophosphatidylcholine is thought to be a characteristic component of the chromaffin granules in adrenal glands. By the use of a t.l.c. system that resolves minor phospholipids satisfactorily, this subcellular location was confirmed in the present study in bovine glands. However, phospholipid degradation was demonstrated in homogenates of the adrenal medulla and cortex under conditions similar to those of subcellular fractionation (incubation at 4 degrees C for 90min). Phosphatidylethanolamine and cardiolipin were hydrolysed, but the concentration of lysophosphatidylcholine did not change, indicating that the latter was present in the medulla before this treatment. Attempts were made to decrease the time between death of the animal and the extraction of lipids. Lysophosphatidylcholine was easily demonstrable in lipid extracts of the dissected medulla and even in those of the whole bovine gland. For practical reasons it is not possible to decrease further the time lapse before extraction in the case of this animal. Adrenal glands were obtained from anaesthetized and untreated rabbits. These were frozen immediately in liquid N(2) and the lipids were extracted. In a control experiment, the glands from rabbit were dissected and treated in the same manner as with those of ox, and then the lipids were extracted. No lysophosphatidylcholine was detected in the extracts from glands frozen in liquid N(2) but lysophosphatidylcholine was observed in the controls. These results suggest that lysophosphatidylcholine is not a component of chromaffin granules, but is produced if the period between death of the animal and lipid extraction is unduly prolonged. To discover whether lysophosphatidylcholine affected the permeability barrier properties of chromaffin granules, sonicated liposomes of egg phosphatidylcholine alone or with lysophosphatidylcholine (15mol/100mol) were prepared. Both types were shown by electron microscopy to be largely made up of single bilayer vesicles. The exchange diffusion of [(14)C]dopamine was measured across their membranes. Both types of liposomes had similar capture volumes (0.5mul/mumol of phospholipid), and the activation energies of the exchange diffusion of dopamine were also similar (31kJ/mol). These results indicate that the presence of this proportion of lysophosphatidylcholine in chromaffin-granule membranes is not likely to influence their barrier properties towards catecholamines.

Adrenal Glands↗
PubMed1977

Mycoplasma-like structures in granulomatous angiitis of the central nervous system. Case reports with light and electron microscopic studies.

Two patients had granulomatous angiitis of the central nervous system. The typical vasculitis involved the small branches of the cerebral arteries in both patients and resulted in thrombosis of the left middle cerebral artery in one. Electron microscopy demonstrated structures resembling Mycoplasma organisms. These were present in small numbers in the wall and in the granulomatous reaction within the lumen. Giant cells were observed cintaining particles suggestive of Mycoplasma within the perinuclear cisternae. Virus-like particles were not observed.

Adult↗
PubMedDate not supplied

Metabolism of alkyl lysophospholipid in epithelial cancer cell lines and inhibition of cell growth.

The mechanism of inhibition of cancer cell growth by alkyllysophospholipids is not known. We have investigated the metabolism of 1-O-octadecyl-2-O-methylglycerophosphocholine (ET-18-OCH3) in MCF7, A427, and A549 cell lines to determine whether there is a correlation between metabolism and sensitivity and whether the growth-inhibitory effects are due to ET-18-OCH3 or its metabolites. After 12 h incubation with ET-18-OCH3, less than 1.5% of ET-18-OCH3 taken up in the cells was converted to 1-O-octadecyl-2-O-methylglycerol (OMG). No correlation was observed between the extent of metabolism and sensitivity to the compound. Incubation of cells with 1 microgram OMG/mL (2.8 microM) for 12 h resulted in cellular quantities of OMG in MCF7, A427, and A549 that were, respectively, 8-, 5-, and 25-fold greater than those in cells incubated with 5 micrograms ET-18-OCH3/mL (9.6 microM). While 12 h incubation with 1 microgram OMG/mL did not significantly inhibit the proliferation of MCF7 or A427 cells, incubation with 5 micrograms ET-18-OCH3/mL inhibited MCF7 and A427 growth by 90 and 15%, respectively. A549 cell growth was inhibited 10% by 1 microgram OMG/mL, but not by 5 micrograms ET-18-OCH3/mL. Incubation of cells for 12 h with 5 micrograms OMG/mL (13.9 microM) inhibited the growth of all three cell lines. Our results indicate that both ET-18-OCH3 and OMG can inhibit cell growth but the low quantities of OMG produced from ET-18-OCH3 are not responsible for the observed inhibition of MCF7 and A427 cell growth.

Antineoplastic Agents↗
PubMedDate not supplied

The relationship between cellular ether glycerophospholipid content and sensitivity of cancer cells to 1-O-octadecyl-2-O-methyl-glycerophosphocholine.

Cancer cells are more susceptible to the growth-inhibitory effects of alkyl lysophospholipids than normal cells, but the mechanism of this selectivity is unknown. In this study we have investigated the hypothesis that the sensitivity of cells to alkyl lysophospholipids is related to the cellular ether lipid content. The order of decreasing sensitivity of the cells to the growth-inhibitory effect of 1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18-OCH3) was MCF 7 > T84 > Malme 3M > A427 > A549, while the order of decreasing ether phospholipid content as a proportion of the total phospholipid was T84 > A427 = A549 = Malme 3M > MCF7. There was also no correlation between ET-18-OCH3-sensitivity and the proportion of ether lipid in the cholineglycerophospholipid or ethanolamineglycerophospholipid classes. Our results clearly indicate that the postulated relationship between ether phospholipid content and ET-18-OCH3-susceptibility may have very limited applicability and is unlikely to be the underlying reason for the selective effects of alkyl lysophospholipids.

Antineoplastic Agents↗
PubMedDate not supplied

Synthesis of ether-linked analogues of lysophosphatidate and their effect on the proliferation of human epithelial cancer cells in vitro.

To investigate whether lysophosphatidate analogues of alkyllysophospholipids were antiproliferative we synthesized three new ether-linked analogues of lysophosphatidic acid and investigated their antiproliferative activity on epithelial cancer cell lines derived from different tissues. The antiproliferative effects of the compounds on MCF-7 and T47D (breast), A549 and A427 (lung), A498 (kidney), SK-N-SH and SK-N-MC (neuroblastoma), and DU145 (prostate) cells were compared with the ability of 1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine, the archetypic alkyllysophospholipid, to inhibit the proliferation of all the cell lines. 1-O-Hexadecyl-2-O-methyl-sn-glycero-3-phosphate and 4-thiohexadecyl-3(S)-O-methoxybutane-4-phosphate were unable to inhibit the proliferation of any of the cells to any degree, while slightly enhancing the proliferation of DU145 cells. In contrast 4-O-hexadecyl-3(S)-O-methoxybutanephosphonate was a potent antiproliferative agent that was on the whole more active than 1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine. Since 1-Oleoyl-2-lyso-phosphatidate (LPA) was non-mitogenic in all the cell lines except the neuroblastoma line SK-N-SH, it is unlikely that the inhibition of cell proliferation by 4-O-hexadecyl-3(S)-O-methoxybutanephosphonate was a consequence of perturbation of cellular response to the mitogenic effects of LPA.

Antineoplastic Agents↗
PubMedDate not supplied

Glycosylated antitumor ether lipids are more effective against oncogene-transformed fibroblasts than alkyllysophospholipids.

We have investigated the antiproliferative effects of different types of antitumor ether lipids (AELs) against non-transformed and transformed fibroblasts. The compounds examined were choline phosphate-containing alkyllysophospholipids (1-O-octadecyl-2-O-methyl glycerophosphocholine (ET18-OCH3), 2'-(trimethylammonio)ethyl 3-(hexadecyloxy)-2-(methoxymethyl)propylphosphate (oxo-BM 41.440), 2'-(triethylammonio)ethyl 4-(hexadecyloxy)-3-methoxybutane phosphonate (ET16-OCH3-phosphonocholine)), and glycosylated ether-linked diglycerides (1-O-hexadecyl-2-O-methyl-3-S-(beta-D-1'-thioglucopyranosyl-sn-gly cerol) [ET16-OCH3-beta-thio-Glc] and 1-O-hexadecyl-2-O-methyl-3-O-(2'amino-2'-deoxy-beta-D-glucopyranosyl)-sn -glycerol (ET16-OCH3-Gln)). The choline phosphate-containing alkyllysophospholipids (ALPs) had little or moderate effect on the proliferation and none on the viability of NIH 3T3 clone 7, and sublines transformed by raf (NIH/9IV #5), fes (Fes 1), src (Src 1) and mos (Mos 1) oncogenes. The glycosylated ether-linked diglycerides were more effective than the choline phosphate-containing ALPs. Of the two ether-linked diglycerides, ET16-OCH3-beta-thio-Glc did not affect the viability of the cells at any of the concentrations examined while ET16-OCH3-Gln was cytotoxic to all the transformed cell lines at concentrations equal to or greater than 9 microM. The IC50 for ET16-OCH3-Gln was 6.4 microM for Mos 1, 6.5 microM for NIH/9IV #5, 7.5 microM for Src 1, 8.2 microM for Fes 1 and 8.4 microM for NIH 3T3 clone 7. These results suggest that the ether-linked diglycerides may be more effective against fibrosarcomas than the cholinephosphate containing ALPs. Also, with the exception of ET16-OCH3-Gln there was no significant difference in the effect of the compounds on the transformed and untransformed cell lines, suggesting that the selectivity displayed by AELs may depend on both the type of compound and transformation in the cell.

3T3 Cells↗