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91.
Aimonetti JM Vedel JP Schmied A Pagni S 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2000,133(3):391-401
The question of whether Ia reciprocal inhibition might depend on the motor task and on the type of motor unit activated was investigated in the human extensor carpi radialis muscles. Ia reciprocal inhibition induced by stimulating the median nerve (conditioning stimulation) was estimated by measuring the changes in the firing probability of 37 extensor motor units in response to the radial nerve stimulation (100 test stimuli) delivered 1 ms after the conditioning stimulation. Six subjects were asked to perform a task consisting of either selectively contracting their wrist extensor muscles or co-activating their wrist and finger antagonist muscles by clenching their hand around a manipulandum. In the control recordings (test stimulation alone), the mean response probability of the 37 motor units was found to be greater during hand clenching. The motor units were identified on the basis of their force thresholds, their macro-potentials, and their twitch contraction times. The data obtained in the control recordings were consistent with the size principle. In the recordings where the responses were conditioned by applying median nerve stimulation, the response probability of the motor units with low force thresholds, small macro-potential areas, and long twitch contraction times tended to decrease, in line with the presence of Ia reciprocal inhibition, whereas the response probability of the motor units with higher force thresholds, larger macro-potential areas, and shorter twitch contraction times tended to increase. The median nerve stimulation may therefore have altered the efficiency with which the extensor Ia inputs recruited the homonymous motoneurones in the pool. The flexor group I afferents activated while the median nerve was stimulated had inhibitory effects on the slow contracting motor units, and facilitatory effects mainly on the fast contracting motor units. Both of these effects were stronger during hand clenching, in which the numerous cutaneous receptors of the palm and fingertips are liable to be activated. Besides their own effects on the excitability of the various types of motor units, cutaneous inputs are known to potentiate the Ib interneurones. In addition, the effects of the conditioning stimulation were superimposed on the tonic activity of the Ia and Ib afferents from the flexor wrist and finger muscles. This may explain why both the inhibitory and facilitatory effects of the median nerve stimulation were enhanced during hand clenching. 相似文献
92.
In the spinal cord dorsal horn, presynaptic GABAA receptors (GABAARs) in the terminals of nociceptors as well as postsynaptic receptors in spinal neurons regulate the transmission of nociceptive and somatosensory signals from the periphery. GABAARs are heterogeneous and distinguished functionally and pharmacologically by the type of α subunit variant they contain. This heterogeneity raises the possibility that GABAAR subtypes differentially regulate specific pain modalities. Here, we characterized the subcellular distribution of GABAAR subtypes in nociceptive circuits by using immunohistochemistry with subunit‐specific antibodies combined with markers of primary afferents and dorsal horn neurons. Confocal laser scanning microscopy analysis revealed a distinct, partially overlapping laminar distribution of α1–3 and α5 subunit immunoreactivity in laminae I–V. Likewise, a layer‐specific pattern was evident for their distribution among glutamatergic, γ‐aminobutyric acid (GABA)ergic, and glycinergic neurons (detected in transgenic mice expressing vesicular glutamate transporter 2–enhanced green fluorescent protein [vGluT2–eGFP], glutamic acid decarboxylase [GAD]67–eGFP, and glycine transporter 2 (GlyT2)–eGFP, respectively). Finally, all four subunits could be detected within primary afferent terminals. C‐fibers predominantly contained either α2 or α3 subunit immunoreactivity; terminals from myelinated (Aβ/Aδ) fibers were colabeled in roughly equal proportion with each subunit. The presence of axoaxonic GABAergic synapses was determined by costaining with gephyrin and vesicular inhibitory amino acid transporter to label GABAergic postsynaptic densities and terminals, respectively. Colocalization of the α2 or α3 subunit with these markers was observed in a subset of C‐fiber synapses. Furthermore, gephyrin mRNA and protein expression was detected in dorsal root ganglia. Collectively, these results show that differential GABAAR distribution in primary afferent terminals and dorsal horn neurons allows for multiple, circuit‐specific modes of regulation of nociceptive circuits. J. Comp. Neurol. 520:3895–3911, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
93.
Collombet JM Four E Fauquette W Burckhart MF Masqueliez C Bernabé D Baubichon D Lallement G 《Neurotoxicology》2007,28(1):38-48
Gliotic scar formation and angiogenesis are two biological events involved in the tissue reparative process generally occurring in the brain after mechanically induced injury, ischemia or cerebral tumor development. For the first time, in this study, neo-vascularization and glial scar formation were investigated in the brain of soman-poisoned mice over a 3-month period after nerve agent exposure (1.2 LD50 of soman). Using anti-claudin-5 and anti-vascular endothelial growth factor (VEGF) immunostaining techniques on brain sections, blood vessels were quantified and VEGF expression was verified to appraise the level of neo-angiogenesis induced in damaged brain areas. Furthermore, glial scar formation and neuropathology were estimated over time in the same injured brain regions by anti-glial fibrillary acidic protein (GFAP) immunohistochemistry and hemalun-phloxin (H&P) dye staining, respectively. VEGF over-expression was noticed on post-soman day 3 in lesioned areas such as the hippocampal CA1 field and amygdala. This was followed by an increase in the quantity of mature blood vessels, 3 months after soman poisoning, in the same brain areas. On the other hand, massive astroglial cell activation was demonstrated on post-soman day 8. Reactive astroglial cells were located only in damaged cerebral regions where H&P-stained eosinophilic neurons were found. For longer experimental times, astroglial response slowly decreased overtime but remained detectable on post-soman day 90 in some discrete brain regions (i.e. CA1 field and amygdala) evidencing the formation of a glial scar. In this study, we discuss the key role of VEGF in the angiogenic process and in the glial or neuronal response induced by soman poisoning. 相似文献
94.
Disruption of glutamate homeostasis frequently leads to oxidative stress and to the release of hydroxyl radicals (radical OH). Here, we investigated, via a microdialysis approach, the possible involvement of metabotropic glutamate receptors in the glutamate-induced release of hydroxyl radicals in adult rat striatum. Glutamate was applied at low amount, resulting in a moderate release that was not inhibited by dizocilpine (MK-801), a specific NMDA receptor antagonist. (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a broad spectrum metabotropic antagonist, that does not exert any effect on the basal release of radical OH suppressed their response to glutamate. (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD), a non-selective metabotropic glutamate receptors agonist, promoted an radical OH release almost similar to that observed after glutamate, which was similarly impaired by co-infusion with MCPG. By contrast, infusion of (RS)-3,5-dihydroxyphenylglycine (DHPG), a more specific group I metabotropic glutamate receptors agonist, did not result in any appreciable radical OH response. Thus, beside NMDA receptors, some metabotropic glutamate receptors may also be involved in the glutamate-induced release of hydroxyl radicals. 相似文献
95.
96.
Meghari S Rolain JM Grau GE Platt E Barrassi L Mege JL Raoult D 《The Journal of infectious diseases》2006,193(3):380-386
BACKGROUND: Bartonella quintana, the etiological agent of bacillary angiomatosis (BA), causes endothelial cell proliferation. Erythromycin has dramatic effects on BA, and the effects are largely unexplained by the compound's bacteriostatic properties. Our aim here was to evaluate the possibility that erythromycin alters angiogenesis. METHODS: The effect of erythromycin on B. quintana-induced endothelial cell proliferation was studied using a wild-type strain and an erythromycin-resistant B. quintana mutant. The latter was generated by serial subcultures on blood agar plates. RESULTS: We show that erythromycin significantly inhibits the proliferation of dermal microvascular endothelial cells induced either by wild-type B. quintana or by our erythromycin-resistant mutant. Doxycycline and gentamycin failed to exert such an effect. Finally, we found that the resistant strain harbored a 27-bp insertion in the highly conserved region of the gene encoding the ribosomal protein L4; this insertion may explain the existence of the resistance to erythromycin. CONCLUSION: The data presented here indicate that erythromycin profoundly down-modulates endothelial cell proliferation irrespective of its bacteriostatic effects and suggest that this may be a key component of the efficacy of the compound in the treatment of patients with BA. 相似文献
97.
Gerhard Schumann Roberto Bonora Ferruccio Ceriotti Georges Férard Carlo A Ferrero Paul F H Franck F Javier Gella Wieland Hoelzel Poul J?rgen J?rgensen Takashi Kanno Art Kessner Rainer Klauke Nina Kristiansen Jean-Marc Lessinger Thomas P J Linsinger Hideo Misaki Mauro Panteghini Jean Pauwels Fran?oise Schiele Heinz G Schimmel Gerhard Weidemann Lothar Siekmann 《Clinical chemistry and laboratory medicine》2002,40(7):718-724
This paper is the fourth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 2. 相似文献
98.
Disruption of the gene homologous to mammalian Nramp1 in Mycobacterium tuberculosis does not affect virulence in mice 下载免费PDF全文
Boechat N Lagier-Roger B Petit S Bordat Y Rauzier J Hance AJ Gicquel B Reyrat JM 《Infection and immunity》2002,70(8):4124-4131
Natural-resistance-associated macrophage protein 1 (Nramp1) is a divalent cation transporter belonging to a family of transporter proteins highly conserved in eukaryotes and prokaryotes. Mammalian and bacterial transporters may compete for essential metal ions during mycobacterial infections. The mycobacterial Nramp homolog may therefore be involved in Mycobacterium tuberculosis virulence. Here, we investigated this possibility by inactivating the M. tuberculosis Nramp1 gene (Mramp) by allelic exchange mutagenesis. Disruption of Mramp did not affect the extracellular growth of bacteria under standard conditions. However, the Mramp mutation was associated with growth impairment under conditions of limited iron availability. The Mramp mutant displayed no impairment of growth or survival in macrophages derived from mouse bone marrow or in Nramp1(+/+) and Nramp1(-/-) congenic murine macrophage cell lines. Following intravenous challenge in BALB/c mice, counts of parental and Mramp mutant strains were similar in the lungs and spleens of the animals at all time points studied. These results indicate that Mramp does not contribute to the virulence of M. tuberculosis in mice. 相似文献
99.
Pyrethroid-treated nets are an efficient tool for reducing malaria transmission and morbidity. The recent evolution of pyrethroid resistance in several Anopheles species represents a major threat for the future success of roll back malaria in Africa. The possible use of nonpyrethroid insecticides, such as carbamates, on nets is a promising alternative solution because these insecticides are effective against susceptible and pyrethroid-resistant populations of Anopheles and Culex mosquitoes. Unfortunately, carbamate resistance as a result of insensitive acetylcholinesterase has recently been detected in Anopheles gambiae s.s. populations from C?te d'Ivoire. Using biochemical assays on surviving Anopheles mosquitoes from an experimental hut trial, we showed evidence for selection for an insensitive acetylcholinesterase mechanism by carbamate impregnated bednets. However, no such selection has been found with nets treated with pyrethroid alone or pyrethroid/carbamate "two-in-one" -treated nets. Because pyrethroid-impregnated nets were suspected to select for the Kdr mutation in An. gambiae, we propose that use of two-in-one nets could be a promising alternative strategy for the management of insecticide resistance in malaria vectors. 相似文献
100.
Guillet B Lambert T d'Oiron R Proulle V Plantier JL Rafowicz A Peynet J Costa JM Bendelac L Laurian Y Lavergne JM 《Human mutation》2006,27(7):676-685
Hemophilia A (HA) is an X‐linked hereditary bleeding disorder defined by a qualitative and/or quantitative factor VIII (FVIII) deficiency. The molecular diagnosis of HA is challenging because of the high number of different causative mutations that are distributed throughout the large F8 gene. The putative role of the novel mutations, especially missense mutations, may be difficult to interpret as causing HA. We identified 95 novel mutations out of 180 different mutations responsible for HA in 515 patients from 406 unrelated families followed up at a single hemophilia treatment center of the Bicêtre university hospital (Assistance Publique‐Hôpitaux de Paris [AP‐HP], Le Kremlin‐Bicêtre). These 95 novel mutations comprised 55 missense mutations, 12 nonsense mutations, 11 splice site mutations, and 17 small insertions/deletions. We therefore developed a mutation analysis based on a body of proof that combines the familial segregation of the mutation, the resulting biological and clinical HA phenotype, and the molecular consequences of the amino acid (AA) substitution. For the latter, we studied the putative biochemical modifications: its conservation status with cross‐species FVIII and homologous proteins, its putative location in known FVIII functional regions, and its spatial position in the available FVIII 3D structures. The usefulness of such a strategy in interpreting the causality of novel F8 mutations is emphasized. Hum Mutat 27(7), 676–685, 2006. © 2006 Wiley‐Liss, Inc. 相似文献