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101.
Control of interneurone firing pattern by axonal autoreceptors in the juvenile rat cerebellum 总被引:2,自引:0,他引:2
Recent work has shown that certain neurones have axonal GABAA receptors, whose tonic activation modifies their firing properties and neurotransmitter release capability. In addition, results obtained in interneurones of the molecular layer of the cerebellum indicate that action potential-released GABA binds back to the axon that released it, generating an autoreceptor current. In the present paper, we show that at physiological Cl− i concentration (15 m m ) and at 34–36°C, the autoreceptor current generates a large amplitude (up to 21 mV) afterdepolarization that lasts for about 150 ms, and that occasionally leads to double firing. Furthermore we show that elimination of the afterdepolarization, by either blocking GABAA receptors, or eliminating the autoreceptor currents through prolonged whole-cell recording, decreases burst firing. I h (a hyperpolarization-activated current) was previously found to be prominent in interneurone axons. We show that blocking I h leads to an increase in the amplitude of the autoreceptor current as well as of the associated afterdepolarization, suggesting a shunting effect of I h on autoreceptor-mediated afterdepolarization. Conversely, blocking I h accentuates burst firing. The effects of autoreceptor-mediated afterdepolarization on firing are prominent during a period of development when interneurone synapses are stabilized and vanish by postnatal day 17 (PN 17), together with the expression of the autoreceptor current. Altogether, this work reveals a new role for autoreceptors in the regulation of cell excitability and firing pattern, which may contribute to the development and stabilization of the cerebellar network. 相似文献
102.
Philippe Hup Cline Rouveirol Isabel Brito Pierre Neuvial Philippe La Rosa Eric Viara Nicolas Stransky Gaëlle Pierron Elodie Mani Caroline Brennetot Isabelle Jannoueix Nadge Gruel Alain Aurias Olivier Delattre Franois Radvanyi Emmanuel Barillot 《European journal of medical genetics》2005,48(4):467-468
103.
Association of DLG5 R30Q variant with inflammatory bowel disease 总被引:6,自引:0,他引:6
Daly MJ Pearce AV Farwell L Fisher SA Latiano A Prescott NJ Forbes A Mansfield J Sanderson J Langelier D Cohen A Bitton A Wild G Lewis CM Annese V Mathew CG Rioux JD 《European journal of human genetics : EJHG》2005,13(7):835-839
Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system known as the inflammatory bowel diseases (IBD). Recently, Stoll and colleagues reported a novel finding of genetic variation in the DLG5 gene that is associated with IBD (CD and UC combined). We present here a study of the genetic variation described in that report in two well-powered, independent case-control cohorts and one family-based collection, and confirm the proposed association between IBD and the R30Q variant of DLG5 in two of the three studies. We are, however, unable to replicate the other proposed association to the common haplotype described in Stoll et al and suggest that this other finding could conceivably have been partially a statistical fluctuation and partially a result of LD with the replicated R30Q association. This study provides support for the hypothesis that DLG5 constitutes a true IBD risk factor of modest effect. 相似文献
104.
Dien Pham Huy Monique Roch-Arveiller Monique Lenoir Olivier Muntaner Alain Thuret Jean-Paul Giroud 《Inflammation research》1986,18(3-4):366-371
The effect of piroxicam on rat polymorphonuclear leucocytes (PMN) has been studiedin vitro andin vivo after the induction of two acute, non specific inflammatory reactions (pleurisies induced by calcium pyrophosphate crystals (CaPP) or isologous serum).An inhibition of chemotaxis by piroxicam has been demonstrated by two techniques, the filter and agarose assaysin vivo andin vitro. An inhibition of random cell migration has been observed only at the higher drug concentration using agarose assay with CaPP-elicited cells.Piroxicam also inhibited superoxide anion generation and O2 consumption of CaPP- and serum-elicited cells.These findings suggest that piroxicam may have a direct effect on PMN responses and that this activity could, at least in part, contribute to its anti-inflammatory properties. 相似文献
105.
Brémond-Gignac D Gérard-Blanluet M Copin H Bitoun P Baumann C Crolla JA Benzacken B Verloes A 《American journal of medical genetics. Part A》2005,134(4):422-425
The WAGR contiguous gene deletion syndrome is a combination of Wilms tumor, Aniridia, Genito-urinary abnormalities, and growth and mental retardation which is invariably associated with an 11p13 deletion. We report two monozygotic twins and a third, unrelated patient with WAGR syndrome and additional clinical features not usually associated with WAGR. Both twins had developmental delay, growth deficiency, severe ocular involvement (nystagmus, aniridia, cataracts), atrial septal defect and two uncommon findings: agenesis of the corpus callosum and duplication of the halluces. One twin developed Wilms tumors aged 19 months while her sister remained tumor free by the age of 6.5 years. The singleton patient showed typical WAGR syndrome and preaxial hallucal polydactyly. Molecular cytogenetic studies refined the identification of the extent of the deleted segments, which were not identical in the two families. The two deletions included the PAX6 and WT1 genes as previously reported in typical WAGR patients. The unusual anomalies described in this report, may represent the expression of low penetrant traits associated with haploinsufficency of one or more of the genes present in the deletion (PAX6 is expressed in CNS) or may indicate epistatic influences of modifier genes on the expression of gene(s) present in the WAGR region. 相似文献
106.
Batard T Didierlaurent A Chabre H Mothes N Bussières L Bohle B Couret MN Ball T Lemoine P Focks Tejkl M Chenal A Clément G Dupont F Valent P Krauth MT André C Valenta R Moingeon P 《International archives of allergy and immunology》2005,136(3):239-249
BACKGROUND: We describe the production in Escherichia coli as a recombinant protein of clinical grade wild-type Bet v 1a (rBet v 1a), to be used as a candidate vaccine against birch pollen allergy. METHODS: This recombinant protein was purified by hydrophobic interaction and ion exchange chromatography and characterized by SDS-PAGE, immunoprint and circular dichroism in parallel with natural Bet v 1 (nBet v 1) purified from a birch pollen extract. We also compared rBet v 1 and nBet v 1 for their capacity to induce histamine release from basophils and to stimulate T lymphocyte proliferation. RESULTS: rBet v 1a appears in SDS-PAGE as an 18-kDa monomeric protein, whereas purified nBet v 1 comprises a mixture of isoforms (resolving as three distinct bands and six spots after 1-dimensional and 2-dimensional electrophoresis, respectively). Both recombinant and natural purified Bet v 1 molecules are recognized by IgE from birch pollen-allergic patients as well as anti-Bet v 1 murine monoclonal antibodies, suggesting that the recombinant protein is correctly folded in a native configuration. Circular dichroism analysis confirmed that the two Bet v 1 molecules exhibit similar 3-dimensional structures, even if rBet v 1a appears more compact and stable in thermodenaturation/renaturation experiments. Both rBet v 1 and nBet v 1 induce the degranulation of sensitized basophils and proliferation of Bet v 1-specific T lymphocytes in a similar manner. CONCLUSIONS: On the basis of these structural and biological properties, rBet v 1a is a valid candidate vaccine against birch pollen allergy, currently evaluated in humans. 相似文献
107.
Blouquit S Sari A Lombet A D'herbomez M Naline E Matran R Chinet T 《American journal of respiratory cell and molecular biology》2003,29(2):245-251
Endothelin-1 (ET-1) exerts many biological effects in airways, including bronchoconstriction, airway mucus secretion, cell proliferation, and inflammation. We investigated the effect of ET-1 on Na absorption and Cl secretion in human bronchial epithelial cells. Addition of 10(-7) M ET-1 had no effect on the inhibition of the short circuit current (Isc) induced by amiloride, a Na channel blocker. Addition of 10(-7) M ET-1 to the apical bath in the presence of amiloride increased Isc in cultured human bronchial epithelial cells studied in Ussing chambers. No effect was observed when ET-1 was added to basolateral bath, indicating that the involved ET-1 receptors are likely present only in the apical membrane of the cells. Use of Cl-free solutions and bumetanide reduced the ET-1-induced increases in Isc, indicating that ET-1 stimulates Cl secretion. The ET-1-induced increase in Isc was prevented by exposure to the ETB receptor antagonist BQ-788 but not to the ETA receptor antagonist BQ-123. ET-1 did not raise intracellular Ca levels, but increased the intracellular concentration of cAMP. These findings indicate that ET-1 is a Cl secretagogue in human airways and acts presumably through apically located ETB receptors and activation of the cAMP pathway. 相似文献
108.
Morse MA Garst J Osada T Khan S Hobeika A Clay TM Valente N Shreeniwas R Sutton MA Delcayre A Hsu DH Le Pecq JB Lyerly HK 《Journal of translational medicine》2005,3(1):9-8
BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1-2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52-665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors. 相似文献
109.
Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene 总被引:2,自引:0,他引:2
Feldmann D Denoyelle F Loundon N Weil D Garabedian EN Couderc R Joannard A Schmerber S Delobel B Leman J Journel H Catros H Ferrec C Drouin-Garraud V Obstoy MF Moati L Petit C Marlin S 《European journal of human genetics : EJHG》2004,12(4):279-284
Mutations in GJB2 are the most common cause of congenital nonsyndromic hearing loss. The controversial allele variant M34T has been hypothesized to cause autosomal dominant or recessive nonsyndromic hearing impairment and some in vitro data has been consistent with this hypothesis. In this report, we present the clinical and genotypic study of 11 families (seven familial forms of nonsyndromic sensorineural hearing loss (NSSNHL) and four sporadic cases) in which the M34T GJB2 variant has been identified. The M34T mutation did not segregate with the deafness in six of the seven familial forms of NSSNH. Eight persons with normal audiogram presented a heterozygous M34T variation and five normal hearing individuals were composite heterozygous for M34T and another GJB2 mutation. Four normal hearing individuals with a documented audiogram were M34T/35delG and one was M34T/(GJB6-D13S1830)del. Screening a French control population of 116 subjects we have found an M34T allele frequency of 1.72%. This percentage was not significatively different from the prevalence of the M34T allele in the deaf population, which was 2.12%. All these data suggest that the M34T variant is not clinically significant in human and is a frequent polymorphism in France. 相似文献
110.
Schindler I Rice NJ McIntosh RD Rossetti Y Vighetto A Milner AD 《Nature neuroscience》2004,7(7):779-784
When we reach out to pick something up, our arm is directed to the target by visuomotor networks in the cortical dorsal stream. However, our reach trajectories are influenced also by nontarget objects, which might be construed as potential obstacles. We tested two patients with bilateral dorsal-stream (parietal lesions, both of whom were impaired at pointing to visual stimuli (optic ataxia). We asked them to reach between two cylinders, which varied in location from trial to trial. We found that the patients' reaches remained invariant with changes in obstacle location. In a control task when they were asked to point midway between the two objects, however, their responses shifted in an orderly fashion. We conclude that the dorsal stream provides the visual guidance we automatically build into our movements to avoid potential obstacles, as well as that required to ensure arrival at the target. 相似文献