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991.
Duga S Asselta R Bonati MT Malcovati M Dalprà L Oldani A Zucconi M Ferini-Strambi L Tenchini ML 《Epilepsia》2002,43(4):362-364
Twenty-four autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) probands were analyzed for the presence of V287L and V287M mutations in the CHRNB2 gene, which have been recently associated with the disease. In all patients, the involvement of the two additional loci reported as being associated with ADNFLE (CHRNA4 gene and chromosome 15q24 region) had been previously excluded. Mutational screening was performed by sequencing a polymerase chain reaction-amplified CHRNB2 DNA fragment, spanning the whole exon 5, which contains the V287L and V287M mutations and codes for approximately 65% of the mature protein. In none of the patients were mutations in the analyzed region of CHRNB2 found. These data, obtained in the largest ADNFLE cohort so far analyzed, demonstrate the rarity of the identified CHRNB2 mutations in ADNFLE patients. 相似文献
992.
Overactivation of N-methyl-D-aspartate (NMDA) glutamate receptors is closely related to epilepsy and excitotoxicity, and the phosphorylation of these receptors may facilitate glutamate-mediated synaptic transmission. Here we show that in awake rats the microinjection into the hippocampus of okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A, induces in about 20 min intense electroencephalographic and behavioral limbic-type seizures, which are suppressed by the systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine hydrogen maleate and by the intrahippocampal administration of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, an inhibitor of protein kinases. Two hours after okadaic acid, when the EEG seizures were intense, an increased serine phosphorylation of some hippocampal proteins, including an enhancement of the serine phosphorylation of the NMDA receptor subunit NR2B, was detected by immunoblotting. Twenty-four hours after okadaic acid a marked destruction of hippocampal CA1 region was observed, which was not prevented by the receptor antagonists. These findings suggest that hyperphosphorylation of glutamate receptors in vivo may result in an increased sensitivity to the endogenous transmitter and therefore induce neuronal hyperexcitability and epilepsy. 相似文献
993.
Piłkowska E Jakubowska T Witkowska K Kulczycki J 《Neurologia i neurochirurgia polska》2002,36(6):1075-1085
25 patients with neurological and neuropsychological deficits after a mild ischaemic stroke were treated with nicergoline (Adavin 60 mg/d) versus placebo in a double blind cross-over trial (3 and 3 months). The patients were examined repeatedly by a neurologist and a neuropsychologist using a battery of tests (PPL, AVLT, Benton and Bourdon tests, number-repetition test). On completion of the trial the improvement of neurological signs (mainly cerebellar deficits) and neuropsychological impairments (in particular of attention and manual manipulation difficulties) was found to be more marked after the period of nicergoline treatment than after placebo. No drug-dependent side effects--including the influence on blood pressure--were observed in the whole group treated. 相似文献
994.
Wattanasirichaigoon D Swoboda KJ Takada F Tong HQ Lip V Iannaccone ST Wallgren-Pettersson C Laing NG Beggs AH 《Neurology》2002,59(4):613-617
The alpha-tropomyosin-3 (TPM3) gene was screened in 40 unrelated patients with nemaline myopathy (NM). A single compound heterozygous patient was identified carrying one mutation that converts the stop codon to a serine and a second splicing mutation that is predicted to prevent inclusion of skeletal muscle exon IX. TPM3 mutations are a rare cause of NM, probably accounting for less than 3% of cases. The severity of cases with TPM3 mutations may vary from severe infantile to late childhood onset, slowly progressive forms. 相似文献
995.
Stokes AH Freeman WM Mitchell SG Burnette TA Hellmann GM Vrana KE 《Neurotoxicology》2002,23(6):675-684
Dopamine (DA) metabolism and oxidation produce both reactive oxygen species (ROS) and reactive quinones. These chemical species are implicated in dopamine neurotoxicity and neurodegeneration. In the present studies, human neuroblastoma (SK-N-SH) cells were exposed to toxic concentrations of dopamine (333 microM) in order to investigate molecular pathways involved in dopamine toxicity. cDNA hybridization array (microarray) technology demonstrated that GADD45 and GADD153 (growth arrest and DNA-damage inducible) gene expression was increased in dopamine-treated cells (333 microM for 18 h). Subsequent Northern and Western blot analysis confirmed these changes in GADD45 and GADD153 gene expression. The antioxidant, ascorbic acid, significantly reduced the increase in GADD45 gene expression but did not significantly reduce GADD153 gene expression. Currently, the precise function of the GADD gene products is not known. It is known, however, that these genes are upregulated in response to stress to allow cells time to repair macromolecular damage. In the present case, GADD gene expression (manifested as increased mRNA and protein levels) preceded dopamine-induced cytotoxicity. It appears that dopamine, through the formation of reactive oxygen species and quinones, may damage cellular macromolecules to the point of inducing GADD gene expression. Other genes that displayed changes, but that have not been subjected to post-hoc confirmation, include clusterin (increased), ubiquitin (increased), CD27 ligand (increased), CD27BP (increased), and rac-PK-beta (decreased). 相似文献
996.
Antisense oligonucleotides are short pieces of synthetic, chemically modified DNA or RNA that are designed to interact by Watson-Crick base pairing with mRNA encoding a targeted protein. During the past 20 years the technology associated with the development of antisense has improved dramatically, and emerging chemistries have made antisense oligonucleotides into powerful and versatile tools to study the function of proteins in living cells. The dramatic increase in novel genomic sequence information that has recently become available has generated enormous opportunities for the development of antisense oligonucleotides capable of altering the expression level of virtually any gene. With this will come a nearly equal opportunity to determine the role of individual proteins in a vast array of cardiovascular disease. The great specificity that these compounds exhibit in vitro suggests that they may also have an exciting future for development into therapeutics useful for the treatment of human disease. This review highlights some of the advances made in the field of antisense research, placing an emphasis on uses and proper controls. 相似文献
997.
998.
Evidence for endogenous agmatine in hypothalamo-neurohypophysial tract and its modulation on vasopressin release and Ca2+ channels 总被引:2,自引:0,他引:2
Wang G Gorbatyuk OS Dayanithi G Ouyang W Wang J Milner TA Regunathan S Reis DJ 《Brain research》2002,932(1-2):25-36
Agmatine, decarboxylated from arginine by arginine decarboxylase, is particularly prominent in the hypothalamus. The present study utilized the rat hypothalamo-neurohypophysial system to determine expression and "pre-synaptic" modulation of agmatine in the central nervous system (CNS). Under confocal-laser scanning, agmatine-like immunoreactivity (Agm-LI) was found enriched in arginine-vasopressin (AVP)-containing magnocellular neurons of the supraoptic nuclei (SON) and paraventricular nuclei (PVN). In addition, using electron microscopy, Agm-LI was found closely associated with large neurosecretory-like vesicles in neurohypophysial nerve terminals of posterior pituitary gland. Radioimmunoassay revealed that 10 and 30 microM agmatine concentration-dependently inhibited the depolarization-evoked AVP release from isolated neurohypophysial terminals. Using perforated patch-clamp, effects of agmatine on whole-terminal voltage-gated ion currents in the isolated neurohypophysial nerve terminals were examined. While it did not significantly affect either tetrodotoxin (TTX)-sensitive Na(+) or sustained Ca(2+)-activated K(+) channel currents, agmatine (1-40 microM) inhibited Ca(2+) channel currents in approximately 53% of the total nerve terminals investigated. The onset of inhibitory effect was immediate, and the inhibition was reversible and concentration-dependent with an IC(50)=4.6 microM. In the remaining (approximately 47%) neurohypophysial nerve terminals, only a higher (120 microM) concentration of agmatine could moderately inhibit Ca(2+) channel currents. The results suggest that: (1) endogenous agmatine is co-expressed in AVP-containing, hypothalamic magnocellular neurons of the SON/PVN and in neurohypophysial nerve terminals of posterior pituitary gland; (2) agmatine may serve as a physiological neuromodulator by regulating the voltage-gated Ca(2+) channel and, as a result, the release of AVP from neurohypophysial nerve terminals. 相似文献
999.
1000.
Alves CR Delucia R Silva MT 《Progress in neuro-psychopharmacology & biological psychiatry》2002,26(6):1089-1093
The effects of fencamfamine (FCF), an indirect dopamine (DA) agent, were investigated using the latent inhibition (LI) model of schizophrenia. In the LI procedure, rats preexposed (PE) to an unreinforced stimulus show difficulty in subsequent learning of an association in which that stimulus is predictive of an unconditioned stimulus (US). FCF (1.75, 3.5 and 7.0 mg/kg i.p.) yielded an inverse dose-response relationship regarding LI. At 3.5 mg/kg, LI was abolished and no effect was observed at 1.75 and 7.0 mg/kg. The effect of FCF (3.5 mg/kg) on LI was blocked by the antipsychotic risperidone (RIS; 4.0 mg/kg), a D2/5HT2 antagonist. These results confirm the similarity of the behavioral profile of FCF and amphetamine (AMPH). In addition, they provide a further validation of the LI model for psychosis, since RIS was shown to prevent a psychostimulant-induced disruption of LI. 相似文献