Search PubMed⌕ Search

Biomedical subjects

D Bertrand

Publications and source records attributed to D Bertrand.

At least 73 records · Page 4Linked to original sources
PubMed1999

No evidence for linkage between schizophrenia and markers at chromosome 15q13-14.

Freedman et al. [1997: Proc Natl Acad Sci USA 94:587-592] reported linkage in nine multiplex schizophrenia families to markers on chromosome 15, using impaired neuronal inhibition to repeated auditory stimuli (P50), a neurophysiological deficit associated with schizophrenia, as the phenotype. The highest LOD score obtained (5.3 at theta = 0) was for marker D15S1360 mapped to chromosome 15q13-14, less than 120 kb from the alpha7-nicotinic receptor (CHRNA7) gene. The study also reported a small positive LOD score for D15S1360 when examined for linkage to the schizophrenia phenotype. Following these findings, we examined three polymorphic markers (D15S1360, L76630, and ACTC) on chromosome 15q13-14 near the CHRNA7 gene for linkage to schizophrenia, using 54 pedigrees from an independent study. Alleles for these three markers were genotyped and analyzed using parametric and nonparametric methods. No LOD score above 1.00 was obtained for any marker, and affected sib-pair analysis likewise showed no evidence for linkage. We conclude that in our families the region around the CHRNA7 locus does not contain a major locus for susceptibility to schizophrenia.

Chromosomes, Human, Pair 15↗
PubMed1999

Synaptic transmission at nicotinic acetylcholine receptors in rat hippocampal organotypic cultures and slices.

1. Whole-cell clamp recordings of the compound synaptic current elicited by afferent stimulation of Schaffer collaterals showed that blockade of the NMDA, AMPA and GABAA receptor-mediated components by 6-nitro-7-sulphamoyl- benzo(f)quinoxaline-2,3-dione (NBQX), 3-((R)-2-carboxypiperazine-4-yl)propyl-1-phosphonate (R-CPP) and picrotoxin, respectively, left a small residual current in 39 out of 41 CA1 pyramidal neurones in organotypic cultures and 9 out of 16 CA1 cells in acutely prepared slices. 2. This current represented 2. 9 +/- 0.4 % of the compound evoked synaptic response in organoypic cultures and 1.4 +/- 0.5 % in slices. It was characterized by a slightly rectifying I-V curve and a reversal potential of 3.4 +/- 5. 1 mV. 3. This residual current was insensitive to blockers of GABAB, purinergic, muscarinic and 5-HT3 receptors, but it was essentially blocked by the nicotinic receptor antagonist d-tubocurarine (91 +/- 4 % blockade; 20 microM), and partly blocked by alpha-bungarotoxin (200 nM) and methyllycaconitine (10 nM), two antagonists with a higher selectivity for alpha7 subunit-containing nicotinic receptors (48 +/- 3 % and 55 +/- 11 % blockade, respectively). 4. The residual current was of synaptic origin, since it occurred after a small delay; its amplitude depended upon the stimulation intensity and it was calcium dependent and blocked by the sodium channel antagonist tetrodotoxin. 5. We conclude that afferent stimulation applied in the stratum radiatum evokes in some hippocampal neurones a small synaptic current mediated by activation of neuronal nicotinic receptors.

Aconitine↗
PubMed1999

Molecular basis of the charge selectivity of nicotinic acetylcholine receptor and related ligand-gated ion channels.

Nicotinic acetylcholine receptors are homo- or heteropentameric proteins belonging to the superfamily of receptor channels including the glycine and GABA-A receptors. Affinity labelling and mutagenesis experiments indicated that the M2 transmembrane segment of each subunit lines the ion channel and is coiled into an alpha-helix. Comparison of the M2 sequence of the cation-selective alpha 7 nicotinic receptor to that of the anion-selective alpha 1 glycine receptor identified amino acids involved in charge selectivity. Mutations of the alpha 7 homo-oligomeric receptor within (or near) M2, namely E237A, V251T and a proline insertion P236' were shown to convert the ionic selectivity of alpha 7 from cationic to anionic. Systematic analysis of each of these three mutations supports the notion that the conversion of ionic selectivity results from a local structural reorganization of the 234-238 loop. The 234-238 coiled loop, previously shown to lie near the narrowest portion of the channel, is thus proposed to contribute directly to the charge selectivity filter. A possible functional analogy with the voltage-gated ion channels and related receptors is discussed.

Amino Acid Sequence↗
PubMed1999

Modulation of synaptic transmission by nicotine and nicotinic antagonists in hippocampus.

Using rat hippocampal slices, we studied the effects of nicotine and three antagonists of neuronal nicotinic receptors on excitatory and inhibitory transmission. We report that nicotine at concentrations between 0.5 and 100 microM enhanced excitatory synaptic responses and increased the size of the presynaptic fiber volley. This effect was reproduced by three neuronal nicotinic receptor antagonists: dihydro-beta-erythroidine, methyllycaconitine and mecamylamine. In contrast, nicotine, but not nicotinic antagonists, produced a dual effect on inhibition: nicotine enhanced gamma-aminobutyric-acid A (GABA(A)) receptor-mediated synaptic responses at low concentration (0.5 microM) and blocked them at high concentration (100 microM). We conclude that the excitatory effects of nicotine are reproduced by nicotinic receptor antagonists, thereby suggesting that these effects might be mediated through receptor desensitization. These results also indicate that nicotine differentially affects GABAergic inhibition at low and high concentrations-effects that are not reproduced by antagonists.

Aconitine↗
PubMed1999

Mutational analysis of the charge selectivity filter of the alpha7 nicotinic acetylcholine receptor.

In the alpha7 nicotinic acetylcholine receptors, we analyze the contribution of mutations E237A and V251T, together with the proline insertion P236', in the conversion of the charge selectivity from cationic to anionic. We show that the triple mutant exhibits spontaneous openings displaying anionic selectivity. Furthermore, at position 251, hydrophilic or even negatively charged residues are compatible with an anionic channel. In contrast, the additional proline yields an anionic channel only when inserted between positions 234 and 237; insertion before 234 yields a cationic channel and after 238 alters the receptor surface expression. The coiled 234-238 loop thus directly contributes to the charge selectivity filter of the alpha7 channel.

Amino Acid Sequence↗
PubMed1999

Adonia variegata (Coleoptera: Coccinellidae) bears maternally inherited flavobacteria that kill males only.

Inherited bacteria that parasitically distort the pattern of sex allocation of their host, biasing allocation towards female progeny, are found in many arthropods. One such manipulation is male-killing, where male progeny of infected females die during embryogenesis. We here provide evidence for a male-killing bacterium in the coccinellid beetle, Adonia variegata. We then address 3 questions. First, is this male-killing bacterium one that is found in other hosts, or does it represent a new transition to male-killing within the eubacteria? Using the sequence of the 16S rDNA of the bacterium, we found that the male-killing bacterium is a member of the Flavobacteria--Bacteroides group, most closely related to the male-killing bacterium in another ladybird beetle, Coleomegilla maculata. Secondly, is there any evidence that this bacterium affects female host physiology? In a paired test under nutritional stress, we found no evidence for a physiological benefit to infection, and weak evidence of a physiological cost, in terms of reduced fecundity. Thirdly, is there any evidence of host involvement in the transmission of the bacterium to the germ line? We found no evidence of host involvement. Rather, bacteria migrated to the ovariole independently of host cells. We conclude that the bacterium is a parasite, and discuss how 2 different species of ladybird come to be infected with 1 lineage of bacterium, and why case studies of male-killing bacteria have generally found little evidence of any symbiont contribution to host physiological functioning.

Animals↗
PubMed1999

Invasion of one insect species, Adalia bipunctata, by two different male-killing bacteria.

Male-killing bacteria, which are inherited through the female line and kill male progeny only, are known from five different orders of insect. Our knowledge of the incidence of these elements has stemmed from discovery of their phenotype in different species. Our estimate of the frequency with which insects have been invaded by these elements therefore depends on each observation of the male-killing phenotype within a species being associated with a single microorganism. We here record an example of a single insect species being infected with two taxonomically distinct male-killing bacteria. Western European populations of the two-spot ladybird, Adalia bipunctata, have previously been shown to bear a male-killing Rickettsia. However, we here show that the majority of the male-killing lines tested from Central and Eastern Europe do not bear this bacterium. Rather, 16S rDNA sequence analysis suggests male-killing is associated with a member of the genus Spiroplasma. We discuss this conclusion in relation to the evolutionary genetics of male-killing bacteria, and the evolution of male-killing behaviour in the eubacteria.

Animals↗
PubMed1999

Presence of functional neuronal nicotinic acetylcholine receptors in brainstem motoneurons of the rat.

In mammals, nicotinic acetylcholine receptors (nAChRs) play a crucial role in motor control. Muscle-type nAChRs mediate synaptic excitation of skeletal muscle by motoneurons, and nAChRs are present on Renshaw cells, where they produce recurrent inhibition of spinal motoneurons. We asked whether nAChRs are also present in motoneurons. Whole-cell recordings were performed on various motor nuclei in brainstem slices of young rats. Neurons were visualized using infrared (IR) videomicroscopy. Acetylcholine (ACh) or the nicotinic agonist, epibatidine, were delivered by pressure microinjection. Facial (VII), hypoglossal (XII) and vagal (X) motoneurons responded to ACh by generating a fast inward current. In VII motoneurons, the ACh effect was mimicked by epibatidine, and nicotine induced a slow inward current and desensitized the ACh-evoked current. In VII and XII motoneurons, the ACh-evoked current was blocked by the nicotinic antagonist dihydro-beta-erythroidine (DHbetaE), but was unaffected by methyllycaconitine (MLA), an alpha7-specific antagonist. By contrast, the ACh-induced current in X motoneurons was sensitive to MLA. Current-voltage relationships indicated that the currents mediated by either alpha7-containing (X) or non-alpha7-containing (VII, XII) nAChRs displayed inward rectification. In accordance with the electrophysiological data, autoradiography revealed that VII, X and XII nuclei of young rats contained binding sites for [3H]epibatidine; binding sites for [125I]alpha-bungarotoxin, a selective ligand of alpha7-containing nAChRs, were present in X nucleus but were almost undetectable in VII and XII nuclei. Thus, brainstem motoneurons of young rats possess functional nAChRs. They could promote fast synaptic coupling between motoneurons, and thus play a role in somatic and visceral motor functions.

Animals↗
PubMed1999

Mutated nicotinic receptors responsible for autosomal dominant nocturnal frontal lobe epilepsy are more sensitive to carbamazepine.

PURPOSE: The recent linkage between a genetically transmissible form of epilepsy (ADNFLE) and mutations within the alpha4 subunit, one component of the major brain neuronal nicotinic acetylcholine receptor (nAChR), raises the question of the role of this receptor in epileptogenesis. Although acting by different mechanisms, the two genetic alterations so far identified both render the nAChR less efficient. In view of the high sensitivity of ADNFLE to carbamazepine (CBZ), we studied the effects of this drug and of valproate (VPA) on the human alpha4beta2 nAChR and its mutations. METHODS: The alpha4beta2 nAChRs from control and mutant alpha4 subunits were reconstituted in Xenopus oocytes and investigated by using a dual-electrode voltage clamp technique. Acetylcholine (ACh)-evoked currents recorded in the absence or presence of antiepileptic drugs (AEDs) were studied to analyze the mode of action of these compounds. RESULTS: ACh-evoked currents at the human alpha4beta2 nAChR were readily and reversibly inhibited by approximately 100 microM CBZ. This compound was found to be a noncompetitive inhibitor of the nAChR, which probably acts by entering the channel and causing a blockade by steric hindrance. Dose-response inhibition curves determined on the control receptor and on ADNFLE-mutant receptors showed a greater sensitivity of the mutants to CBZ, with median inhibitory concentrations (IC50s) in the range of the antiepileptic plasma levels of CBZ. In contrast, VPA had nearly no effect on control and mutant nAChRs. CONCLUSIONS: CBZ inhibits the neuronal alpha4beta2 nAChRs at pharmacologic concentrations, with ADNFLE mutants displaying about threefold higher sensitivity to this compound. The increased sensitivity of these mutant receptors supports the hypothesis that the antiepileptic activity of CBZ can, at least to some extent, be attributed to the nAChR inhibition.

Animals↗
PubMed1999

[A quality reference manual for radiology].

The purpose of this article is to introduce a quality manual for radiology departments. A radiology department has implemented a quality improvement program since 1996. This manual was developed as a tool for quality improvement program. This manuscript, was based on foreign accreditation manuals as well as from French experiences and summarized. In addition, new criteria were added, especially in the field of interventional radiology. This reference book is first dedicated to the self-assessment of radiology departments. It can also be used for an external audit.

Accreditation↗
PubMed1999

Neuronal nicotinic acetylcholine receptors: their properties and alterations in autosomal dominant nocturnal frontal lobe epilepsy.

Identification of genes coding for the neuronal nicotinic acetylcholine receptors (nAChRs) has allowed rapid progress in the field of neuroscience. Determination of a high-affinity binding site for nicotine that correlates with the expression of mRNAs coding for nAChRs as well as protein expression is the best demonstration for localization of these receptors. Reconstitution of functional nAChRs in cells following cDNAs injection opened new ways to study these receptors in isolation. Furthermore, the recent linkage analysis between a form of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) with a mutation in the gene coding for the alpha 4 subunit of the neuronal nAChRs constituted the first demonstration that alteration of these receptors may be at the origin of epileptic discharges. Physiological and pharmacological studies of these mutated receptors revealed that the two mutations so far identified in ADNFLE patient cause a loss of function. In this work we shall review, in the light of the latest findings, properties of control and mutated receptors and evaluate how their alteration can be at the origin of nocturnal seizures.

Epilepsy, Frontal Lobe↗
PubMed1999

[Physicians' opinions and practices on the use of medical referrals at hospitals].

This work aims to take stock of the actual utilisation of medical standards (references), through a study of opinions and practices of the medical managers working in the clinical services of a university hospital centre. A survey through interviews was proposed to 103 medical managers, 101 responded to the questionnaire (38 Unit directors and 63 directors of "UF" units). Medical standards are used essentially as a teaching aid by 80% of doctors. Some of them (48%) make them available to prescribing doctors in the unit, and for 36% there exists an informational procedure for new residents. Evaluation studies concerning the implementation of medical standards remain rare (7 studies). Medical standards appear to be more useful for improving quality of care (90%) then for controlling health expenditures (72%). The majority of medical managers (72%) consider that certain standards should be opposable to hospitals. The medical managers of the university hospital centre are in favour of developing standards of clinical practice.

France↗
PubMed1999

[Effectiveness of a program for improving drug prescriptions and hospitalization reporting at a university hospital].

OBJECTIVES: To evaluate the effectiveness of a method for improving the quality of care applied to the formulation of medical prescriptions and to the release of hospitalisation reports. The actions comprised the diffusion of results of audits and recommendations of good practice. METHODS: For each of the 41 services, 30 visits from 1996 were selected at random. 3289 prescriptions and 1067 correspondence files were analyzed. The results were compared to those obtained from the previous two years. RESULTS: Patient identification was complete in 44% of prescriptions, the identification of the prescribing doctor and his signature were present in 62% and 19% of cases respectively. 37% of medicines included all information. 7 indicators out of 12 for the quality of prescriptions improved (p < 0.0001). Files were found for 83% of hospital visits and 56% were sent (released) within a week. The practitioner was identified in 79% of cases, the main diagnosis in 96% and the treatment in 65% of cases. Five out of nine indicators of the quality of correspondence improved (p < 0.01). For each theme, the number of indicators improving was similar (p > 0.05). The services that improved for one theme didn't necessarily improve for the second (p > 0.05). DISCUSSION: The evaluation of the programme, based on a strategy of quality assurance, shows modest progress. Given that the improvement of two themes for a given service are not correlated, the programme appears to sensitise professionals at an individual level rather than collectively. However, this programme is an important step for introducing a mode of continued improvement of quality.

Drug Prescriptions↗