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Ouabain-insensitive salt and water movements in duck red cells. II. Norepinephrine stimulation of sodium plus potassium cotransport 总被引:2,自引:9,他引:2 下载免费PDF全文
Catecholamines induce net salt and water movements in duck red cells incubated in isotonic solutions. The rate of this response is approximately three times greater than a comparable effect observed in 400 mosmol hypertonic solutions in the absence of hormone (W.F. Schmidt and T. J. McManus. 1977 a.J. Gen. Physiol. 70:59-79. Otherwise, these two systems share a great many similarities. In both cases, net water and salt movements have a marked dependence on external cation concentrations, are sensitive to furosemide and insensitive to ouabain, and allow the substitution of rubidium for external potassium. In the presence of ouabain, but the absence of external potassium (or rubidium), a furosemide-sensitive net extrusion of sodium against a large electrochemical gradient can be demonstrated. When norepinephrine-treated cells are incubated with ouabain and sufficient external sodium, the furosemide-sensitive, unidirectional influxes of both sodium and rubidium are half- maximally saturated at similar rubidium concentrations; with saturating external rubidium, the same fluxes are half-maximal at comparable levels of external sodium. In the absence of sodium, a catecholamine-stimulated, furosemide-sensitive influx of rubidium persists. In the absence of rubidium, a similar but smaller component of sodium influx can be seen. We interpret these results in terms of a cotransport model for sodium plus potassium which is activated by hypertonicity or norepinephrine. When either ion is absent from the incubation medium, the system promotes an exchange-diffusion type of movement of the co-ion into the cells. In the absence of external potassium, net movement of potassium out of the cell leads to a coupled extrusion of sodium against its electrochemical gradient. 相似文献
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Sander A Huisman Wendy Bijman-Lagcher Jan NM IJzermans Ron Smits Ron WF de Bruin 《Cell cycle (Georgetown, Tex.)》2015,14(14):2333-2339
Irinotecan is a widely used topoisomerase-I-inhibitor with a very narrow therapeutic window because of its severe toxicity. In the current study we have examined the effects of fasting prior to irinotecan treatment on toxicity and anti-tumor activity. FabplCre;Apc15lox/+ mice, which spontaneously develop intestinal tumors, of 27 weeks of age were randomized into 3-day fasted and ad libitum fed groups, followed by treatment with a flat-fixed high dose of irinotecan or vehicle. Side-effects were recorded until 11 days after the start of the experiment. Tumor size, and markers for cell-cycle activity, proliferation, angiogenesis, and senescence were measured. Fasted mice were protected against the side-effects of irinotecan treatment. Ad libitum fed mice developed visible signs of discomfort including weight loss, lower activity, ruffled coat, hunched-back posture, diarrhea, and leukopenia. Irinotecan reduced tumor size in fasted and ad libitum fed groups similarly compared to untreated controls (2.4 ± 0.67 mm and 2.4 ± 0.82 mm versus 3.0 ± 1.05 mm and 2.8 ± 1.08 mm respectively, P < 0.001). Immunohistochemical analysis showed reduced proliferation, a reduced number of vascular endothelial cells, and increased levels of senescence in tumors of both irinotecan treated groups. In conclusion, 3 days of fasting protects against the toxic side-effects of irinotecan in a clinically relevant mouse model of spontaneously developing colorectal cancer without affecting its anti-tumor activity. These results support fasting as a powerful way to improve treatment of colorectal carcinoma patients. 相似文献
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Efficient estimation of the prevalence of multiple rare traits 总被引:1,自引:0,他引:1
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Nucleotide variation in the triosephosphate isomerase (Tpi) locus of Drosophila melanogaster and Drosophila simulans 总被引:3,自引:0,他引:3
Hasson E; Wang IN; Zeng LW; Kreitman M; Eanes WF 《Molecular biology and evolution》1998,15(6):756-769
DNA sequence variation in a 1.1-kb region including the coding portion of
the Tpi locus was examined in 25 homozygous third-chromosome lines of
Drosophila melanogaster, nine lines of Drosophila simulans, and one line of
Drosophila yakuba. Our data show that the widespread allozyme polymorphism
observed in cosmopolitan D. melanogaster is due to a glutamic acid
substitution occurring in a phylogenetically conserved lysine that has been
identified as part of the "hinged-lid" active site of the enzyme. This
observation suggests that the replacement polymorphism may have important
functional consequences. One replacement polymorphism was also observed in
D. simulans, although its functional relevance is more difficult to assess,
since it affects a site that is not strongly conserved. This amino acid
change in D. simulans is associated with a single lineage possessing seven
unique silent substitutions, which may be indicative of balancing selection
or population subdivision. The absence of fixed amino acid differences
between D. melanogaster and D. simulans and only a single difference with
D. yakuba suggests that triose phosphate isomerase is under strong
functional constraint. Silent variation is slightly higher for D.
melanogaster than for D. simulans. Finally, we outline the general lack of
evidence for old balanced polymorphisms at allozyme loci in D.
melanogaster.
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Restriction-map variation associated with the G6PD polymorphism in natural populations of Drosophila melanogaster 总被引:10,自引:0,他引:10
Restriction-map variation was studied in 126 copies of the G6pd region in X
chromosome lines of Drosophila melanogaster from North America, Europe, and
Africa. Special attention was focused on the distribution of variation
relative to the geographically variable polymorphism for two
electrophoretic variants. Nucleotide heterozygosity as determined by eight
six-cutter restriction enzymes for the 13-kb region is estimated, on the
basis of the worldwide sample, to be 0.065%, which is the lowest value
reported for any comparable region in the D. melanogaster genome.
Significant linkage disequilibrium between electrophoretic alleles and
restriction-site variation is observed for several sites. In contrast to
published studies of other genetic regions, there are large insertions that
reach significant frequencies and are found across considerable geographic
distances. There is a clustering of this variation inside the first large
intervening sequence of the G6PD gene.
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Ouabain-insensitive salt and water movements in duck red cells. I. Kinetics of cation transport under hypertonic conditions 总被引:4,自引:6,他引:4 下载免费PDF全文
Duck red cells in hypertonic media experience rapid osmotic shrinkage followed by gradual reswelling back toward their original volume. This uptake of salt and water is self limiting and demands a specific ionic composition of the external solution. Although ouabain (10(-4)M) alters the pattern of cation accumulation from predominantly potassium to sodium, it does not affect the rate of the reaction, or the total amount of salt or water taken up. To study the response without the complications of active Na-K transport, ouabain was added to most incubations. All water accumulated by the cells can be accounted for by net salt uptake. Specific external cation requirements for reswelling include: sufficient sodium (more than 23 mM), and elevated potassium (more than 7 mM). In the absence of external potassium cells lose potassium without gaining sodium and continue to shrink instead of reswelling. Adding rubidium to the potassium- free solution promotes an even greater loss of cell potassium, yet causes swelling due to a net uptake of sodium and rubidium followed by chloride. The diuretic furosemide (10(-3)M) inhibits net sodium uptake which depends on potassium (or rubidium), as well as inhibits net sodium uptake which depends on sodium. As a result, cell volume is stabilized in the presence of this drug by inhibition of shrinkage, at low, and of swelling at high external potassium. The response has a high apparent energy of activation (15-20 kcal/mol). We propose that net salt and water movements in hypertonic solutions containing ouabain are mediated by direct coupling or cis-interaction, between sodium and potassium so that the uphill movement of one is driven by the downhill movement of the other in the same direction. 相似文献
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Evidence of independent gene duplications during the evolution of archaeal and eukaryotic family B DNA polymerases 总被引:1,自引:0,他引:1
Eukaryotes and archaea both possess multiple genes coding for family B DNA
polymerases. In animals and fungi, three family B DNA polymerases, alpha,
delta, and epsilon, are responsible for replication of nuclear DNA. We used
a PCR-based approach to amplify and sequence phylogenetically conserved
regions of these three DNA polymerases from Giardia intestinalis and
Trichomonas vaginalis, representatives of early-diverging eukaryotic
lineages. Phylogenetic analysis of eukaryotic and archaeal paralogs
suggests that the gene duplications that gave rise to the three replicative
paralogs occurred before the divergence of the earliest eukaryotic
lineages, and that all eukaryotes are likely to possess these paralogs. One
eukaryotic paralog, epsilon, consistently branches within archaeal
sequences to the exclusion of other eukaryotic paralogs, suggesting that an
epsilon-like family B DNA polymerase was ancestral to both archaea and
eukaryotes. Because crenarchaeote and euryarchaeote paralogs do not form
monophyletic groups in phylogenetic analysis, it is possible that archaeal
family B paralogs themselves evolved by a series of gene duplications
independent of the gene duplications that gave rise to eukaryotic paralogs.
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