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Combi R Dalprà L Malcovati M Oldani A Tenchini ML Ferini-Strambi L 《Brain research bulletin》2004,63(5):353-359
Mutations responsible for autosomal dominant nocturnal frontal lobe epilepsy have been identified in two members of the neuronal nicotinic acetylcholine receptor gene family: CHRNA4(ENFL1 locus) and CHRNB2 (ENFL3 locus) coding for alpha4 and beta2 subunit, respectively. However, mutations in these genes account for only a minority (less than 10%) of cases. For a third ADNFLE locus (ENFL2) on chromosome 15q24 the gene was not identified. The involvement of the three loci in the pathogenesis of ADNFLE was investigated in 12 unrelated Italian families, selected on the basis of anamnestic and video-polysomnographic data. Compliant family members were typed for polymorphic markers spanning the analyzed chromosome regions. Linkage analyses excluded association of all chromosome regions with ADNFLE in 72% of cases. In two, four and one families it was impossible to ascertain or exclude association with ENFL1, ENFL2, or ENFL3, respectively, however, no mutations have been detected in the nicotinic receptor genes located in these regions. These data strongly suggest that ENFL1, ENFL2 and ENFL3 are minor loci for the disease and point to the existence of at least a fourth locus for ADNFLE. 相似文献
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Gamberale R Galmarini CM Fernández-Calotti P Jordheim L Sánchez-Avalos J Dumontet C Geffner J Giordano M 《Biochemical pharmacology》2003,66(11):2185-2191
Administration of the adenosine analogue fludarabine (FLU) in vivo induces a profound and prolonged T lymphopenia which mainly affects CD4(+) cells. To better understand the mechanistic basis underlying this preferential depletion, we analyzed the in vitro susceptibility of T cell subsets to FLU-induced apoptosis. Contrasting with observations in vivo, our results showed that treatment of peripheral blood mononuclear cells with FLU induced a higher level of apoptosis in CD8(+) than in CD4(+) T lymphocytes. This increased sensitivity of CD8(+) T cells to FLU was observed in samples from both, healthy donors and B cell chronic lymphocytic leukemia patients, and resulted in higher CD4:CD8 ratios in FLU-treated than in untreated cultures (P<0.01). Expression of factors involved in FLU transport and metabolism was then evaluated by quantitative real time-PCR in normal T cell subsets. It was found that mRNA levels of human equilibrative nucleoside transporter-1 nucleoside transporter were higher whereas deoxycytidine kinase and IMP/GMP selective 5'-nucleotidase mRNA levels were lower in CD4(+) cells. However the dCK/cN-II ratio was 2-fold greater in CD8(+) than in CD4(+) T lymphocytes, which could account for the higher apoptosis levels observed in the CD8(+) subset. These results favor the view that decreased CD4:CD8 ratios in FLU-treated patients should be attributed to differences in cell recovery and/or homing between T cell subsets. 相似文献
115.
Cellular bases of the antitumor activity of a 7-substituted camptothecin in hormone-refractory human prostate carcinoma models 总被引:2,自引:0,他引:2
116.
NMDA-NR1 and -NR2B subunits mRNA expression in the hippocampus of rats tolerant to Diazepam 总被引:1,自引:0,他引:1
The development of tolerance to the hypolocomotor effects of Diazepam (DZ) is thought to be a contingent or learning phenomenon. In previous reports, we demonstrated a positive correlation between the development of tolerance to the sedative effects of DZ and hippocampal synaptic plasticity. Furthermore, previous exposure to the drug administration context blocks both the tolerance to sedative effects of DZ and the increased hippocampal plasticity. The results of the present investigation show that the development of tolerance to hypolocomotor action of DZ (5 mg/kg/day) for 4 days results in a significant increase in the hybridization signals for mRNA for N-methyl-D-aspartate (NMDA) glutamatergic receptor NR1 and NR2B subunits in the hippocampal dentate gyrus. Furthermore, we have observed more benzodiazepine binding sites in the hippocampus of non-tolerant animals. We conclude that the increased hippocampal synaptic efficacy in DZ tolerant rats, may be NMDA receptor dependent due to an increased recombinant NR1-NR2B complex observed in the hippocampal formation of tolerant rats. 相似文献
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For human beings trace elements are essential nutrients with a gamut of functions. They are for instance indispensable components of many enzymes, so they have some regulatory functions and they may affect immune reactions and free radical generation. Abnormalities of trace elements are primarily the result of uremia, and they may be further modified and sometimes greatly exacerbated by the dialysis procedure. The role of trace elements in hemodialysis (HD) patients has not yet been fully characterized. To prevent some complications in chronic HD patients, it is very important to regulate the levels of trace elements by adequate water treatment. Reverse osmosis is able to prevent the accumulation of the majority of trace elements in the patients. Zinc supplementation may be recommended for patients with proven zinc deficiency, but for all chronic renal failure patients it is questionable. Selenium deficiency is to be suspected in dialyzed patients and selenium supplementation may be beneficial (increasing glutathione peroxidase activity, cardioprotective effect, immunostimulatory properties) for chronic renal failure patients. Supplementation with a trace element may be indicated when its depletion was unequivocally documented and when there is evidence of the positive effects of this element on the quality of life of the dialyzed patients. 相似文献
120.
N B Gordovskaia T N Krasnova L A Braun V Knotková K Nemecek 《Terapevticheski? arkhiv》1990,62(6):113-117
The authors provide the reported data on renal impairment in mixed cryoglobulinemia (CGE) and 3 own CGE case reports. Renal impairment by the type of rapid-progressing nephritis with episodes of acute renal failure was the major sign in the clinical picture of those cases. 相似文献