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151.
p53-Knockout Mice Are Protected Against the Long-Term Effects of Methamphetamine on Dopaminergic Terminals and Cell Bodies 总被引:3,自引:1,他引:2
Abstract: p53-knockout mice provide a useful model to test the role of p53 in the neurotoxic effects of drugs in vivo. To test the involvement of p53 in methamphetamine (METH)-induced toxicity, wild-type mice, as well as heterozygous and homozygous p53-knockout male mice, were administered four injections of three different doses (2.5, 5.0, and 10.0 mg/kg) of the drug given at 2-h intervals within the space of 1 day. METH caused a marked dose-dependent loss of dopamine transporters in both the striatum and the nucleus accumbens of wild-type mice killed 2 weeks after drug administration. However, this METH-induced decrease in dopamine transporters was attenuated in both homozygous and heterozygous p53-knockout mice, with homozygous animals showing significantly greater protection. The possibility for p53 involvement in METH-induced toxicity was also supported by the observation that METH caused marked increases in p53-like immunoreactivity in the striata of wild-type mice and very little change in heterozygous p53-knockout mice, whereas no p53-like immunostaining was detected in the homozygous p53-knockout mice. Further support for p53 involvement was provided by the fact that METH treatment caused significant decreases in dopamine transporter mRNA and the number of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta and the ventral tegmental area of wild-type but not homozygous p53-knockout mice killed 2 weeks after cessation of METH administration. These results provide concordant evidence for a role of the tumor suppressor, p53, in the long-term deleterious effects of a drug acting on brain dopamine systems. 相似文献
152.
Louis Prusse Yvon C. Chagnon France T. Dionne Claude Bouchard 《Obesity (Silver Spring, Md.)》1997,5(1):49-61
An update of the human obesity gene map up to October 1996 is presented. Evidence from Mendelian disorders exhibiting obesity as a clinical feature, single-gene mutation rodent models, quantitative trait loci uncovered in crossbreeding experiments with mouse, rat, and pig models, association and case-control studies with candidate genes, and linkage studies with genes and other markers is reviewed. All chromosomal locations of the animal loci are converted into human genome locations based on syntenic relationships between the genomes. A complete listing of all these loci reveals that only 4 of the 24 human chromosomes are not yet represented, i.e., 9, 18, 21, and Y. Several chromosome arms are characterized by the presence of several putative loci. The following arms include at least three such loci: 1p, 1q, 3p, 4q, 6p, 7q, 8p, 8q, 11p, 11q, 15q, 20q, and Xq. Studies with negative association and linkage results are also reviewed. 相似文献
153.
Pickering Gisele P.; Fellmann Nicole; Morio Beatrice; Ritz Patrick; Amonchot Aime; Vermorel Michel; Coudert Jean 《Journal of applied physiology》1997,83(4):1300-1306
Pickering, Gisèle P., Nicole Fellmann, BéatriceMorio, Patrick Ritz, Aimé Amonchot, Michel Vermorel, and JeanCoudert. Effects of endurance training on the cardiovascularsystem and water compartments in elderly subjects. J. Appl. Physiol. 83(4): 1300-1306, 1997.Theeffects of endurance training on the water compartments and thecardiovascular system were determined in 10 elderly subjects [age62 ± 2 yr, pretraining maximal oxygen consumption(O2 max)/kg = 25 ± 2 ml · min1 · kg1body wt]. They trained on a cycloergometer 3 times/wk for 16 wk(50-80%O2 max,then 80-85%O2 max). They werechecked at 8 wk, 16 wk, and 4 mo after detraining. Training improvedO2 max (+16%) andinduced plasma volume expansion (+11%). No change in total body water,extracellular fluid, interstitial and intracellular fluid volumes,fat-free mass, and body weight was detected in this small sample withtraining. Body fat mass decreased (2.1 ± 2.2 kg).Echocardiography at rest showed increased fractional shortening andejection fraction and decreased left ventricular end-systolic dimension(P < 0.05). Blood volume expansioncorrelates with cardiac contractility and has an impact on cardiacfunction. These improvements are precarious, however, and arecompletely lost after 4 mo of detraining, when elderly subjects losethe constraints and the social stimulation of the imposed protocol. 相似文献
154.
Ventilation and metabolism among rat strains 总被引:3,自引:0,他引:3
Strohl Kingman P.; Thomas Agnes J.; St. Jean Pamela; Schlenker Evelyn H.; Koletsky Richard J.; Schork Nicholas J. 《Journal of applied physiology》1997,82(1):317-323
Strohl, Kingman P., Agnes J. Thomas, Pamela St. Jean, EvelynH. Schlenker, Richard J. Koletsky, and Nicholas J. Schork. Ventilation and metabolism among rat strains. J. Appl. Physiol. 82(1): 317-323, 1997.We examinedventilation and metabolism in four rat strains with variation in traitsfor body weight and/or blood pressure regulation.Sprague-Dawley [SD; 8 males (M), 8 females (F)], BrownNorway (BN; 10 M, 11 F), and Zucker (Z; 11 M, 12 F) rats were comparedwith Koletsky (K; 11 M, 11 F) rats. With the use of noninvasiveplethysmography, frequency, tidal volume, minute ventilation(E),O2 consumption, andCO2 production were derived atrest during normoxia (room air) and during the 5th minute of exposureto each of the following: hyperoxia (100% O2), hypoxia (10%O2-balanceN2), and hypercapnia (7%CO2-balance O2). Statistical methods probedfor strain and sex effects, with covariant analysis by body weight,length, and body mass. During resting breathing, strain effects werefound with respect to both frequency (BN, Z > K, SD) and tidal volume(SD > BN, Z) but not to E. Sexinfluenced frequency (F > M) alone. Z rats had higher values forO2 consumption,CO2 production, and respiratoryquotient than the other three strains, with no independent effect bysex. During hyperoxia, frequency was greater in BN and Z than in SD orK rats; SD rats had a larger tidal volume than BN or Z rats; Z rats hada greater E than K rats; and M had alarger tidal volume than F. Strain differences persisted duringhypercapnia, with Z rats exhibiting the highest frequency andE values. During hypoxic exposure,strain effects were found to influenceE (SD > K, Z), frequency (BN > K), and tidal volume (SD > BN, K, Z). Body mass was only amodest predictor of E during normoxia, of both E and tidal volume withhypoxia, hypercapnia, or hyperoxia, and of frequency duringhypercapnia. We conclude that strain of rats, more than their body massor sex, has major and different influences on metabolism, the patternand level of ventilation during air breathing, and ventilation duringacute exposure to hypercapnia or hypoxia. 相似文献
155.
Emmanuel Martin Valère Cacheux Hélène Cavé Jean Michel Lapierre Denis Le Paslier Bernard Grandchamp 《Human genetics》1995,96(6):668-670
CDKN4/p27Kip1 is a cyclin-dependent kinase (Cdk) inhibitor implicated in G1 phase arrest, which negatively regulates G1 phase progression in response to TGF, and might represent a tumor suppressor gene. We report here the chromosomal assignment of the human CDKN4 gene to chromosome 12p12.3 in close proximity to highly polymorphic microsatellite markers. 相似文献
156.
Sophie Rousseaux Edith Chevret Michèle Monteil Jean Cozzi Roberte Pelletier Didier Delafontaine Bernard Sèle 《Human genetics》1995,96(6):655-660
The meiotic segregation of chromosomes 14 and 21 was analysed in 1116 spermatozoa from an oligoasthenospermic carrier of a Robsertsonian translocation t(14q21q), and in 16 392 spermatozoa from a control donor, using two-colour fluorescence in situ hybridisation (FISH). Two YAC probes (cloned in yeast artificial chromosomes) specific for regions on the long arms of these chromosomes were co-hybridised. Of the spermatozoa, 12% were unbalanced, resulting from adjacent segregations. Chromosomes X, Y and 1 were also simultaneously detected in 1335 spermatozoa from the same carrier. Whereas gonosomal disomy rates were not significantly different from those of the control donors, disomy 1 were slightly but significantly increased to 0.7%. The diploidy rate was also slightly increased to approximately 1% in the translocation carrier. 相似文献
157.
Cloning and molecular characterization of two genes encoding adhesion proteins involved in Trichomonas vaginalis cytoadherence 总被引:11,自引:2,他引:9
158.
Cells were subjected to a range of 45Ca2+ influx loads with A23187. We measured cell 45Ca2+ with time and A23187 dose, and the apparent 45Ca2+ influxes (≡“J(in,app)”) at Ca2+ steady state. We also measured endogeneous exchangeable and total cell Ca2+, which were 50 and 17–220 μM respectively. The effects of A23187 and Ca2+ on cell ATP, swelling, net Cl− permeability, and cell morphology were measured. These were modest and do not affect our conclusions.J(in,app) 3 × 10−4 [A23187]2.9·[Ca2+(o)]μmoles/l·min with 92–552 μM [Ca2+(o)] (≡ external Ca2+ concentration) and 0–7 μM A23187. J(in,app) was increased an order of magnitude by vanadate and is probably much less than the true influx. The least unlikely explanation found for the high [A23187] exponent, 2.9, was that most of the Ca2+ crossing the membrane is expelled by the pump before it can move deeper into the cell.Calcium pumping increased rapidly in response to increased influx, but the steady state cell 45Ca2+ was approximately proportional to J(in,app) rather than approximately constant between 10 and 120 μmoles/l·min with 184 μM [Ca2+(o)]. This is not the result expected from a simple feedback mechanism.At high A23187 doses the pump appears fully activated resulting in a linear relation between cell/medium 45Ca2+ and [A23187]−2. From the plot we calculated α≡free/total exchangeable Ca2+ = 0.38 ± 0.08 (n = 3) and a maximum pump rate, “Pmax” = 78 μmole/l·min. Pmax is underestimated insofar as J(in,app) is less than the true influx. 相似文献
159.
Jacques Dornand Jean-Claude Bonnafous Jean Favero Agnés Gartner Jean-Claude Mani 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1984,804(4):398-403
It is now well established that human lymphoblastoid cell lines showing immaturity characters display ecto-5′-nucleotidase activities lower than normal levels. A recent paper (Sun, A.S., Holland, J.F. and Ohnuma, T. (1983) Biochim. Biophys. Acta 762, 577–584) mentioned that this phenomenon resulted from the presence of a 5′-nucleotidase inhibitor in these cell lines. We demonstrate here that the use of 5′-[3H]AMP as a substrate, and inadequate analysis of the products formed, led them to a misinterpretation. [3H]Adenosine derived from 5′-[3H]AMP hydrolysis was further transformed into [3H]inosine by the adenosine deaminase activity of the leukemic cell lines tested; [3H]inosine was precipitated with the excess substrate and was not taken into account in the ecto-5′-nucleotidase determination, which led the authors to confuse this adenosine deaminase activity with a 5′-nucleotidase inhibitor. We did not observe 5′-nucleotidase inhibition by leukemic cell cytosol when convenient assay methods were used and showed that the presence of such an inhibitor remains to be established. 相似文献
160.
Luc Cynober Jean-Louis Auget Jean Agneray Ohvanesse G. Ekindjian 《Biochemical and biophysical research communications》1984,123(2):535-542
2-deoxyglucose uptake rates at low sugar concentrations (less than 500 μM) appeared to be lower than those predicted by the Michaelis-Menten model which correctly described higher concentrations. This phenomenon which we will call concentration-dependent transport lag, was also observed for L-glucose uptake which suggest that this phenomenon is carrier-independent. A model involving the perimembrane space is developed which, for L-glucose, gives k1 = 0.931 ± 0.072 × 10?6 l. mg protein?1. minute?1, k2 = 2.97 ± 0.19 × 10?7 l. mg protein?1. minute?1 and So = 88,8 ± 4,3 μM; where k1 is the diffusion constant in the cell membrane, k2 is the diffusion constant in the perimembrane space and So the sugar concentration required in the external medium in order to provide an équivalent sugar concentration in the transport carrier area. 相似文献