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71.
Treatment of MCF7 human mammary carcinoma cells with the nonsteroidal antioestrogens, tamoxifen and clomiphene, leads to a concentration-dependent decrease in cellular proliferation rate which can be resolved into oestrogen-reversible and oestrogen-irreversible components. This became more clearly apparent when cells were treated with the 4-hydroxylated derivatives of these compounds where, because of enhanced affinity for the oestrogen receptor (ER), the dose-response curves for the two components could be separated. Thus treatment with 4-hydroxyclomiphene resulted in a distinct biphasic effect on cell growth. In the concentration range 10(-10)-10(-8) M, cell proliferation was inhibited in a concentration-dependent manner to a maximum of 60-70%, there was no further effect between 10(-8) and 10(-6) M, but at concentrations greater than 10(-6) M there was another concentration-dependent decrease in cell growth. Studies with a series of vinyl-substituted hydroxytriphenylethylenes revealed that in the nanomolar concentration range, where the effects of the drugs could be completely negated by the simultaneous addition of oestradiol, the potency for growth inhibition was highly correlated with affinity for ER. Such data provide strong evidence that in this concentration range the growth inhibitory effects of nonsteroidal antioestrogens are mediated by the intracellular ER. In the micromolar concentration range the effects of antioestrogens are not completely reversed by oestradiol, potency is not well correlated with affinity for either ER or the antioestrogen binding site (AEBS) but the effect is cell cycle phase-specific. Furthermore, the disparity between the affinity for AEBS (0.8-3.3 nM) and the concentration of drug needed for oestrogen-irreversible growth inhibition (greater than or equal to 2.5 microM) argue against a central role for AEBS in mediating this effect. The observation that triphenylethylene antioestrogens are calmodulin antagonists may provide some insight into potential mechanisms for this oestrogen-irreversible effect. Indeed, in identical experiments two phenothiazine calmodulin antagonists inhibited MCF 7 cell proliferation at concentrations greater than or equal to 2.5 x 10(-6) M. Growth inhibition following administration of fluphenazine, perphenazine and triphenylethylene antioestrogens was accompanied by qualitatively similar changes in the cell cycle kinetic parameters, i.e. accumulation in G1 phase at the expense of S phase cells. These data suggest triphenylethylene antagonism of calmodulin activated cellular processes as a potential mechanism for the oestrogen-irreversible effects of the nonsteroidal antioestrogens. 相似文献
72.
George G. Laties 《Physiologia plantarum》1987,69(2):305-312
When treated with ethylene in O2, conditioned potato (Solanum tuberosum L. cv. Russet Burbank) tubers – that is, tubers kept at room temperature for 10 days or more – yield slices that are CN? resistant. Ten % CO2 in the gas mixture not only synergizes the effect of ethylene, but replaces the need for conditioning as well. The response to CO2 is more pronounced with increasing time from harvest. By contrast fresh slices from untreated tubers are CN? sensitive, as are slices from tubers incubated in O2 or O2 plus CO2. The suggestion is made that CN? resistance is constitutive, and that treatment with ethylene/CO2 in O2 confers on potato tuber tissue a resistance to the extensive degradation of membrane phospholipids that normally attends slicing and leads to the loss of CN? resistance. In this connection respiration inhibition by imidazole, an inhibitor of fatty acid α-oxidation, is extensive in slices of untreated tubers, and sharply diminished in slices of ethylene-treated tubers in proportion to their CN? resistance. The coextensive rise of respiration rate and CN? resistance in aged potato slices has led to the presumption that the CN?-resistant path mediates the respiration climax. Accordingly the alkaloid, lycorine, has been considered to inhibit the development of CN? resistance in aging potato slices because it curtails the wound-induced respiration. A comparison was carried out on the effect of lycorine on CN?-sensitive and CN?-resistant fresh slices – the latter obtained from ethylene/CO2-treated tubers. Lycorine suppressed the development of the wound-induced respiration without restricting the development of CN? resistance. 相似文献
73.
Jay Hinton Michel C. M. Pérombelon George P. C. Salmond 《Molecular & general genetics : MGG》1987,207(2-3):466-470
Summary The suicide vector pJB4JI was used to generate a range of Tn5-induced mutants of Erwinia carotovora subsp. carotovora (Ecc). One mutant, HC500, was a cysteine auxotroph which had a non-pectolytic, non-cellulolytic, non-proteolytic phenotype when grown under sulphate-limitation. The cysteine lesion of HC500 was shown to be analogous to the cysB mutation of Escherichia coli. The Ecc-cysB
+ gene product was identified as a protein of Mr 36000. 相似文献
74.
Environmental factors influencing the vertical migration of planktonic rotifers in a hypereutrophic tarn 总被引:4,自引:4,他引:0
The diel vertical migration of planktonic rotifers in a small, hypereutrophic tarn was investigated on four occasions in 1983. When the tarn was isothermal the rotifers were distributed throughout the water column. After stratification, the rotifers were confined to the top 1–2 m of oxygenated water. On all four dates the rotifers were aggregated at specific depths in the water column. On some occasions, the pattern of aggregation changed as the animals performed distinct diurnal migrations. Keratella cochlearis, K. quadrata and Polyarthra vulgaris usually followed the reverse migrations of the phytoplankton. In contrast, the movements of Anuraeopsis fissa were less pronounced and were associated with variations in the depth of the oxycline. 相似文献
75.
Characterization of the chicken oocyte receptor for low and very low density lipoproteins 总被引:9,自引:0,他引:9
The chicken oocyte receptor for low and very low density lipoproteins has been identified and characterized. Receptor activity present in octyl-beta-D-glucoside extracts of oocyte membranes was measured by a solid phase filtration assay, and the receptor was visualized by ligand blotting. The protein had an apparent Mr of 95,000 in sodium dodecyl sulfate-polyacrylamide gels under nonreducing conditions and exhibited high affinity for apolipoprotein B-containing lipoproteins, but not for high density lipoproteins or lipoproteins in which lysine residues had been reductively methylated. Binding of lipoproteins was sensitive to EDTA, suramin, and treatment with Pronase. In these aspects, the avian oocyte system was analogous to the mammalian low density lipoprotein receptor in somatic cells. Furthermore, a structural relationship between the mammalian and avian receptors was revealed by immunoblotting: polyclonal antibodies directed against the purified bovine low density lipoprotein receptor reacted selectively with the 95-kDa chicken receptor present in crude oocyte membrane extracts. 相似文献
76.
The role of extracellular matrix in the migration and differentiation of parietal endoderm from teratocarcinoma embryoid bodies 总被引:3,自引:3,他引:0
Embryoid bodies formed from teratocarcinoma stem cells differentiate an outer layer consisting of parietal and visceral endoderm or of visceral endoderm exclusively. We have previously shown that when these embryoid bodies are plated on collagen-coated substrates a parietal endoderm-like cell migrates onto the substrate, whereas all of the visceral endoderm remains associated with the stem cell mass, suggesting a role for substrate contact in parietal endoderm differentiation. We now identify fibronectin as the migration-promoting component in these cultures, and note that laminin and collagen type IV are 10-fold less effective at promoting both attachment and endoderm outgrowth. The RGDS tetrapeptide (arg-gly-asp-ser) from the cell attachment domain of fibronectin can specifically block attachment and outgrowth on both fibronectin- and laminin-coated substrates. In addition, the involvement of the 140-kD fibronectin receptor is demonstrated using an antibody directed against this molecule. 相似文献
77.
J R Harkema C G Plopper D M Hyde J A St George 《The journal of histochemistry and cytochemistry》1987,35(3):279-286
Inhaled irritants induce secretory cell hyperplasia in nasal epithelium of animals. To characterize this response histochemically it is first important to know the histochemical character and distribution of epithelial mucosubstance in the normal nasal cavity. An automated image analyzing method was used to detect and quantitate acidic, neutral, and sulfated mucosubstances in the epithelium lining the nasal and paranasal airways of eight bonnet monkeys. Tissue sections 2 micron thick from defined regions of these airways were stained with either alcian blue/periodic acid-Schiff to demonstrate acid and neutral mucosubstances or high iron diamine to demonstrate sulfated mucins. Respiratory epithelium covering maxilloturbinates had the largest volume of stainable mucosubstance per unit surface area of basal lamina, whereas the maxillary sinus epithelium had the least. There was a general anteroposterior increase in the quantity of total epithelial mucosubstance along the septal and lateral walls of the nasal cavity, and there was more acidic than neutral mucosubstance in the posterior nasal airway than in the anterior. Epithelial mucosubstance in the maxillary sinus was predominantly neutral. Therefore, we conclude that there are substantial regional quantitative differences in stainable mucosubstances in the primate nasal epithelium which must be considered when examining nasal mucosa for irritant-induced changes in epithelial mucins. 相似文献
78.
Mitochondrial DNA of the extinct quagga: Relatedness and extent of postmortem change 总被引:4,自引:0,他引:4
Russell G. Higuchi Lisa A. Wrischnik Elizabeth Oakes Matthew George Benton Tong Allan C. Wilson 《Journal of molecular evolution》1987,25(4):283-287
Sequences are reported for portions of two mitochondrial genes from a domestic horse and a plains zebra and compared to those published for a quagga and a mountain zebra. The extinct quagga and plains zebra sequences are identical at all silent sites, whereas the horse sequence differs from both of them by 11 silent substitutions. Postmortem changes in quagga DNA may account for the two coding substitutions between the quagga and plains zebra sequences. The hypothesis that the closest relative of the quagga is the domestic horse receives no support from these data. From the extent of sequence divergence between horse and zebra mitochondrial DNAs (mtDNAs), as well as from information about the fossil record, we estimate that the mean rate of mtDNA divergence in Equus is similar to that in other mammals, i.e., roughly 2% per million years. 相似文献
79.
d-Aspartate in Human Brain 总被引:3,自引:3,他引:0
Eugene H. Man George H. Fisher Iris L. Payan Rodolfo Cadilla-Perezrios Nancy M. Garcia Radhika Chemburkar Georgine Arends William H. Frey II 《Journal of neurochemistry》1987,48(2):510-515
The presence of the biologically uncommon D-aspartic acid (D-aspartate) in human brain white matter has been previously reported. The earlier study has now been expanded to include D/L-aspartate ratios from 67 normal brains. The data show that the D-aspartate content increases rapidly from 1 year to approximately 35 years of age, levels off in middle age, and then appears to decrease somewhat. The D-aspartate content in gray matter remains at a consistently low level (half of that found in white matter) throughout the human life span. Within the limitations of current analytical methods, there was no detectable difference in D/L-aspartate ratios in white and gray matter of brains with Alzheimer's disease and several other pathologies when compared with brains of normal subjects. However, the presence of a significant D-aspartate level in white matter during the adult life span may lead to changes in protein configuration related to dysfunctions associated with the aging brain. 相似文献
80.
Arie H. Mulder Francois Hogenboom George Wardeh Anton N. M. Schoffelmeer 《Journal of neurochemistry》1987,48(4):1043-1047
Synaptosomes prepared from rat cerebral cortex and labeled with [3H]noradrenaline (NA) were superfused with calcium-free Krebs-Ringer-bicarbonate medium and exposed to 10 mM K+ plus 0.1 mM Ca2+ so that [3H]NA release was induced. 6,7-Dihydroxy-N,N-dimethyl-2-aminotetralin (TL-99) strongly inhibited synaptosomal K+-induced [3H]NA release (EC50 = 5-10 nM) by activating alpha 2-adrenoceptors. Release was also inhibited (maximally by 40-50%) by morphine (EC50 = 5-10 nM), [Leu5]enkephalin (EC50 = approximately 300 nM), [D-Ala2,D-Leu5]enkephalin (DADLE), and Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) (EC50 values = approximately 30 nM). In contrast to the mu-selective opioid receptor agonists morphine and DAGO, the highly delta-selective agonist [D-Pen2,D-Pen5]enkephalin (1 microM) did not affect [3H]-NA release. Furthermore, the inhibitory effect of DADLE, an agonist with affinity for both delta- and mu-opioid receptors, was antagonized by low concentrations of naloxone. The findings strongly support the view that, like alpha 2-adrenoceptors, mu-opioid receptors mediating inhibition of NA release in the rat cerebral cortex are localized on noradrenergic nerve terminals. 相似文献