Biomedical subjects

Guy Roussel

Publications and source records attributed to Guy Roussel.

3 recordsLinked to original sources

PubMed2006

Immunohistochemical localization of a GHB receptor-like protein isolated from rat brain.

Gamma-hydroxybutyrate (GHB) is a substance derived from the metabolism of GABA and is heterogeneously distributed in various regions of the brain. This compound possesses a neuromodulatory role on several types of synapses, particularly those using GABA as a neurotransmitter. At physiological concentrations, this effect of GHB is mediated via specific receptors that induce neuronal hyperpolarization and bind radioactive GHB with a specific distribution, ontogenesis, kinetics, and pharmacology. A membrane protein that possesses six to seven transmembrane domains and which binds and is activated by micromolar amounts of GHB was recently cloned from rat brain hippocampus. In order to study the regional and cellular distribution of this receptor in rat brain, we selected several specific peptides belonging to the extracellular domains of the receptor to be used as specific immunogens to raise polyclonal antibodies in the rabbit. Among the antisera obtained, one of them gave particularly good results in terms of specificity and reactivity at high dilution. Immunohistochemical analyses, both at the confocal and electron microscopic level, showed receptor protein distribution closely resembling the distribution of GHB high-affinity binding sites, except for cerebellum, where GHB receptor(s) of lower affinity exist(s). In all regions studied the GHB receptor-like protein labeling appears to be distributed specifically in neurons and not in glial cells. At the cellular level the antibody specifically labels dendrites, and no immunoreactivity was detected in presynaptic endings or in axons. Accordingly, electron microscopy reveals strong labeling of postsynaptic densities and of neuronal cytosol.

Animals↗

PubMed2003

Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice.

We studied the immunological basis for the very potent encephalitogenicity of myelin/oligodendrocyte glycoprotein (MOG), a minor component of myelin in the CNS that is widely used to induce experimental autoimmune encephalomyelitis (EAE). For this purpose, we generated a mutant mouse lacking a functional mog gene. This MOG-deficient mouse presents no clinical or histological abnormalities, permitting us to directly assess the role of MOG as a target autoantigen in EAE. In contrast to WT mice, which developed severe EAE following immunization with whole myelin, MOG-deficient mice had a mild phenotype, demonstrating that the anti-MOG response is a major pathogenic component of the autoimmune response directed against myelin. Moreover, while MOG transcripts are expressed in lymphoid organs in minute amounts, both MOG-deficient and WT mice show similar T and B cell responses against the extracellular domain of MOG, including the immunodominant MOG 35-55 T cell epitope. Furthermore, no differences in the fine specificity of the T cell responses to overlapping peptides covering the complete mouse MOG sequence were observed between MOG+/+ and MOG-/- mice. In addition, upon adoptive transfer, MOG-specific T cells from WT mice and those from MOG-deficient mice are equally pathogenic. This total lack of immune tolerance to MOG in WT C57BL/6 mice may be responsible for the high pathogenicity of the anti-MOG immune response as well as the high susceptibility of most animal strains to MOG-induced EAE.

Animals↗

PubMedDate not supplied

Computer-based testing in family practice certification and recertification.

BACKGROUND: The member boards of the American Board of Medical Specialties have agreed to expand the scope of certification to include assessment of medical knowledge, practice-based learning and improvement, patient care, interpersonal and communication skills, systems-based practice, and professionalism. Multiple-choice examinations provide limited ability to assess these dimensions. METHODS: The American Board of Family Practice (ABFP) has developed a computer simulation system to facilitate more comprehensive candidate evaluation. The system consists of a knowledge base, a simulation program to create patient scenarios, an interface for presenting simulations to users, and an administrative database to track candidate performance and interactions with the system. The system uses population distributions for disease states to produce cases and evolves patients in response to candidate interventions, such as pharmacological and nonpharmacological therapies. We use Bayesian belief networks to model patient characteristics and comorbid condition interactions. RESULTS: Simulations have been created for 7 disease states; ultimately simulations will be available for 25 to 30 disease states. Initial testing will take place in regional examination centers but will ultimately use the Internet for convenient access for certification and recertification candidates. CONCLUSION: The ABFP will begin field-testing the system in early 2003 and will include simulations in the certification and recertification examination process in 2004.

Bayes Theorem↗