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Biomedical subjects

M Roger

Publications and source records attributed to M Roger.

At least 55 records · Page 3Linked to original sources
PubMed1998

Neocortical grafting to newborn and adult rats: developmental, anatomical and functional aspects.

This report presents the results of neural transplantation experiments that were designed either to study neural developmental phenomena or to appraise the possible restorative capacity of grafts. The first part of the report deals with the findings of transplantation studies that were performed in newborn recipient rats in an attempt to determine the importance of extrinsic or intrinsic factors in the process of areal cortical differentiation. More precisely, we examined the extent to which extrinsic signals drive the pattern of efferent connections of neurons residing in different cortical areas. In the first experiment, we examined the general distribution pattern of efferents arising from homotopic as compared to heterotopic transplants of embryonic cortical tissue placed into the frontal cortex of newborn rats. Our findings indicated that embryonic occipital neurons transplanted heterotopically into the sensorimotor cortex: (a) only rarely contacted normal targets of the motor cortex, (b) systematically projected towards normal targets of the visual cortex, and (c) distributed fibers to structures normally receiving fibers from both the motor and visual cortex, either exclusively into the visual corticorecipient zone of the structure or into both the visual and motor corticorecipient zones. In the second experiment, we attempted to assess the densities of the spinal projections arising from homotopic or heterotopic transplants implanted into the frontal or occipital cortex of newborn rats. We provided evidence that transplants of embryonic neocortical neurons of frontal origin developed and maintained a spinal cord projection whatever their rostrocaudal position within the host neocortex, whereas transplants of occipital origin did not maintain a significant spinal cord projection in adulthood. Finally, in the third experiment, we analyzed the laminar and tangential distribution of the tectal projections developed by transplants of embryonic occipital cortex placed into the primary or secondary subdivisions of the occipital cortex of newborn rats. Abnormalities in the laminar and/or tangential organization of the tectal distribution of the transplant efferents were systematically found. Using these different transplantation paradigms, we provided increasing evidence that, in their heterotopic location, the embryonic neurons retain some of the developmental characteristics corresponding to their embryonic cortical site of origin. Our findings strongly suggested, therefore, that there is an early specification of neocortical neurons to develop area-specific efferents. In conclusion, converging lines of evidence suggest that regional differences in the neuroepithelium are predetermined early in development, thus leading to cerebral cortex parcellation, as hypothesized by Rakic (1988). In the second part of the report, we describe the results of a series of experiments dealing with the consequences of grafting embryonic cortex into the damaged cortex of adult rats. These effects were examined from an anatomical, metabolic, behavioral, and electrophysiological point of views. The experiments were conducted using either the frontal or the visual cortex as models to appraise the functional integration of the grafts into the motor or visual circuits, respectively. The first study was undertaken to examine the capacity of transplants of embryonic frontal neocortical tissue placed into the frontal cortex of an adult recipient to develop efferents into the host CNS. The results indicated that transplants of fetal neocortex placed into adult CNS had the capacity to develop efferents which seemed to grow over significant distances within the host corpus callosum but, in most cases, failed to penetrate deeply into the gray matter. The density of the efferent projections was, however, far weaker than that seen in newborn hosts. In the second study, the 2-deoxyglucose (2-DG) technique was used to examine the functional integration of hom

Age Factors↗
PubMed1998

Comparative study of the genomic organization of DNA repeats within the 5'-flanking region of the natural resistance-associated macrophage protein gene (NRAMP1) between humans and great apes.

The human NRAMP1 gene located on Chromosome (Chr) region 2q35 is a candidate gene for increased risk of infection by several intracellular macrophage parasites, including M. tuberculosis and M. leprae. In search for a possible mutational hot spot, we have analyzed a 3.5-kb region 5' to NRAMP1 that is highly enriched for DNA repeat sequences. The repeat sequences could be grouped into one Mer element and six Alu elements, representing five Alu subfamilies, that had integrated in the same DNA region during successive rounds of Alu retropositional activity. Comparative sequence analysis of the Alu cluster region in humans, chimpanzee (Pan paniscus), and gorilla (Gorilla gorilla) revealed only modest sequence variability and failed to detect any evidence for genomic instability of the highly repetitive DNA region. These results show that sequence length variants in the Alu-flanking regions as well as nucleotide substitutions are the most common genomic variations even in a region of extreme Alu-clustering. Moreover, the high degree of sequence conservation among three primate species argues against the Alu cluster being the site of frequent genomic rearrangements or other frequent genetic events that might influence NRAMP1 expression.

Animals↗
PubMed1998

Direct contacts between fibers from the ventrolateral thalamic nucleus and frontal cortical neurons projecting to the striatum: a light-microscopy study in the rat.

The aim of the present study was to improve our knowledge of the synaptic organization of one major motor loop, the thalamo-fronto-striate system. We examined, within the motor and sensorimotor (Fr1-3, FL, HL) cortices, the organization of the synaptic articulation between thalamic terminals and fronto-striatal neurons. An anterograde tracer (Phaseolus vulgaris leuco-agglutinin) was used to label the fibers from the ventrolateral (VL) thalamic nucleus and a retrograde tracer (subunit b of the cholera toxin) was employed to label the neurons of the frontal cortex projecting to the dorso-lateral quadrant of the caudate-putamen. Our findings indicated that anterogradely labeled fibers arising from the VL formed appositions, presumably synaptic contacts, with retrogradely labeled corticostriate neurons within layer V and, to a lesser degree, within layer III of the frontal cortex. These direct contacts were axo-somatic or axo-dendritic. These findings suggest that some aspects of the motor control mediated by the thalamo-fronto-striate loop could be partly achieved by monosynaptic circuits.

Animals↗
PubMed1998

Neonatal lesion of the rat's frontal cortex and subsequent transplantation of embryonic frontal cortex: evidence of appropriate synaptic integration of the graft neurons within the host thalamo-fronto-striate circuit.

Previous observations in intact rats have indicated that axons from the ventrolateral thalamic nucleus (VL) establish direct axo-somatic or axo-dendritic contacts onto frontal cortical neurons projecting to the striatum. The embryonic frontal cortex was grafted into the damaged frontal cortex of newborn rats to study the capacity of homotopic transplants to restore the thalamo-fronto-striate pathway. Several months later, grafted neurons projecting to the striatum were identified by injecting a retrograde neurotracer (subunit b of the cholera toxin) into the ipsilateral caudate putamen. In the same animal, axons and terminations from the VL were labeled within the transplant with an anterograde neurotracer (Phaseolus vulgaris leuco-agglutinin) injected into the ipsilateral VL. The findings show that VL axons establish direct synaptic contacts onto grafted neurons projecting to the striatum. Although the synaptic contacts were scarce in the transplants, their organization was similar to that observed in intact rats. The contacts were axo-somatic or axo-dendritic. Our observations for the first time indicate that synaptic contacts are formed in cortical grafts and that fetal frontal cortex is susceptible to develop appropriate synaptic integration within the host thalamo-fronto-striate system.

Animals↗
PubMed1998

Influence of host genes on HIV-1 disease progression.

The role of host genes in the course of HIV-1 infection has been examined in different populations and among all major risk groups. Two extended human lymphocyte antigen (HLA) haplotypes, HLA A1-Cw7-B8-DR3-DQ2 and HLA A11-Cw4-B35-DR1-DQ1, are found to be associated with a faster progression to AIDS. The complement C4 factor and tumor necrosis factor genes of the major histocompatibility complex, as well as the mannose binding protein gene, have also been suggested to influence the outcome of AIDS. The recent discovery that chemokine receptors could serve as cofactors for HIV-1 cell entry has prompted a search for polymorphisms in chemokine receptor genes. A 32 base pair inactivating deletion in the CCR5 gene and a point mutation within the CCR2b gene resulting in a conservative amino acid substitution have been examined and shown to be independently associated with delayed disease progression. Together, these observations strongly support a genetic component in AIDS pathogenesis. This article synthesizes the current state of knowledge about the influence of host genes on HIV-1 disease progression. It provides a summary of all significant association studies reported so far. The role of the allelic polymorphism in these genes is discussed with regard to the immunopathogenesis of AIDS.

Carrier Proteins↗
PubMed1998

Three-month sustained-release form of triptorelin in patients with advanced prostatic adenocarcinoma: results of an open pharmacodynamic and pharmacokinetic multicenter study.

The pharmacodynamics and the pharmacokinetic characteristics of a new longer-acting formulation containing 11.25 mg of triptorelin (Decapeptyl) to be administered every 3 months were evaluated in 14 patients with advanced prostate carcinoma. After one single injection, the mean time to reach the surgical castration testosterone range is 22 days, and this effective testosterone suppression is maintained for the 3-month therapy. After a first plasma surge (35.70 ng/ml) occurring 2.5 h after injection and a rise between day 17 and day 31 (maximum on day 24: 0.32 ng/ml), the mean triptorelin plasma level is stable (0.06 +/- 0.05 ng/ml) and maintained until day 91. This new formulation was well tolerated both locally and systemically.

Adenocarcinoma↗
PubMed1998

Hyperleptinaemia is associated with impaired gonadotrophin response to GnRH during late puberty in obese girls, not boys.

In ob/ob mice, leptin deficiency results in hypogonadotrophic hypogonadism, impaired sexual maturation and infertility, which are all corrected by leptin administration. In humans, pubertal development and menarche are related to the attainment of a critical amount of body fat. To examine whether changes in circulating concentrations of leptin could be a hormonal signal influencing gonadotrophin secretion, we studied 98 adolescents and young adults of both sexes, aged 13-19 years, whose weight varied from normal to massively obese and whose sexual maturation was between Tanner stages 3 and 5. We measured leptin, sex steroids and circulating gonadotrophin concentrations in the basal state and in response to GnRH. In perimenarchial and young adult girls, we found that the LH and FSH responses to GnRH were negatively correlated with body mass index (BMI: r = -0.45 and -0.47 respectively, P < 0.0025) and circulating leptin (r = -0.53 and -0.49 respectively, P < 0.002). Decreased LH and FSH responses to GnRH were associated with increased adiposity and hyperleptinaemia. Our data do not establish, but are consistent with a direct neuroendocrine negative effect of excess leptin on the central reproductive system of obese girls. In boys of comparable adiposity, we found no influence of BMI or leptin on gonadotrophin concentrations, which is another aspect of the sexual dimorphism characterizing human leptin physiology.

Adolescent↗
PubMed1997

Development of the striatal projection from embryonic neurons from the lateral or medial frontal cortex grafted homo- or heterotopically into the medial frontal cortex of newborn rats.

The present study was designed to further investigate the effects of intrinsic or extrinsic influences on the development of the efferent connectivity of frontal neocortical neurons. The lateral or medial parts of the frontal neocortex of embryonic (E) day 16 fetuses were grafted into homo- (medial-to-medial) or heterotopic (lateral-to-medial) position in the medial part of the left frontal cortex of newborn hosts. Three to four months after grafting, a retrograde neurotracer was injected into the dorsomedial or ventrolateral quadrant of the left caudate-putamen (CPU). The ensuing retrograde labeling in the transplants was then compared to that found in an equivalent cortical area in control animals. Medial-to-medial transplants developed a striatal projection whose mediolateral organization conforms to that of the projection arising from the medial part of the intact frontal cortex. The mediolateral distribution of the projection arising from lateral-to-medial transplants was not fundamentally different from that originating from medial-to-medial transplants, a finding which stands in marked contrast with what was found recently [7] with medial-to-lateral transplants. These results indicate that inside the frontal cortex, different subregions are not totally interchangeable, at least in terms of development of efferent connectivity.

Animals↗
PubMed1997

Plasma leptin and acute serotoninergic stimulation of the corticotropic axis in women who are normal weight or obese.

In some recent studies, glucocorticoid treatment was associated with rapid induction of obese (ob) gene expression in adipose tissue of normal rats and in isolated adipocytes. We studied the effect of acute stimulation of the corticotropic axis on plasma leptin, the ob gene product, in 7 women of normal weight and 12 women with obesity. Under double-blind, placebo-controlled conditions, a single 12.5-mg dose of clomipramine, a serotonin uptake inhibitor, was administered intravenously in 15 minutes. Mean basal plasma leptin was increased more than 3-fold in subjects with obesity compared with subjects of normal weight (35.1 +/- 4.9 ng/mL vs. 8.9 +/- 1.4 ng/mL, p = 0.001). Whereas corticotropin (ACTH) and cortisol responses were increased in women who were obese compared with women who were lean, no significant effect of clomipramine infusion was found on plasma leptin concentrations measured during the following 150 minutes in both groups. There was a strong positive correlation between basal plasma leptin concentrations and body mass index (r = 0.92, p < 0.0001). In six subjects with obesity studied after a moderate weight loss, mean basal plasma leptin was significantly decreased (43.7 +/- 6.4 ng/mL before vs. 28.0 +/- 8.1 ng/mL after, p = 0.04), but the hormonal response pattern to clomipramine administration was unchanged. We conclude that, at least in the short term, an acute stimulation of the corticotropic axis does not seem to increase leptin secretion in humans, as shown by the response to the serotoninergic agent clomipramine.

Adolescent↗
PubMed1997

Abnormalities in the development of the tectal projection from transplants of embryonic occipital cortex placed in the damaged occipital cortex of newborn rats.

We have examined the degree of precision in the topographic arrangement of the tectal projection developed by homotopic transplants of embryonic occipital cortex and tried to determine whether the development of the corticotectal projection is exclusively dependent on environmental cues or is also controlled by intrinsic factors. Transplants of embryonic (E16) occipital cortex were grafted into various areas of the occipital cortex (Oc1 or Oc2) of newborn rats and the organization of the tectal projection arising from the transplants was subsequently examined by injecting different neurotracers into the transplants. Our results indicate that in most cases the laminar and tangential distributions of the tectal projections from the transplants were abnormal. Indeed, whatever the location of the transplant in the host occipital cortex and whatever the placement of the injection into the transplant, a hybrid distribution of the tectal labeling was found, reminiscent of the pattern observed following tracer deposits in both Oc1 and Oc2 in intact animals. Since the grafts were composed of cells of both Oc1 and Oc2 embryonic origin, it is likely that the hybrid pattern of efferents reflects the heterogeneity of the embryonic origin of the cells composing the graft. These findings provide evidence that the development of the topographic distribution of neocortical efferents is not only dependent on factors extrinsic to the cortex and further indicate that even within one single cortical region, the occipital cortex, different areas (Oc1 vs Oc2) are not totally interchangeable. These findings might have important implications in transplantation experiments aiming at the reconstruction of damaged neocortical circuitry where a precise "point-to-point" reconstruction of the circuitry is expected.

Animals↗
PubMed1997

A technique based on the use of activated charcoal for easier subsequent retrieval of neocortical grafts placed in the neocortex of newborn rats.

The mechanisms underlying the differentiation of neocortical areas are still largely unknown. The development of neural connectivity constitutes one important step in neocortical differentiation. One way to study the mechanisms guiding this developmental stage is to examine the connections established by transplants of neocortical tissue of varying embryonic age placed in varying areas of the neocortex of newborn hosts. Neurotracer injection into the transplant at different intervals following transplantation is then used to identify the development of host-transplant connectivity. In most cases, however, it is rather difficult to retrieve the transplant within the host cortex even shortly after grafting. Hence, it is very difficult to perform tracer injections limited to the transplant without any involvement of the host cortex. In some instances, the transplant position can be predicted by some weaker vascularization within or at the surface of the graft. This is not, however, a reliable criterion to establish the rostrocaudal and mediolateral coordinates of the tracer injection. In this report, we describe the use of activated charcoal to mark the transplant at the time of transplantation. The transplant containing black dots can subsequently be easily distinguished from the host pale pink cortex.

Animals↗
PubMed1997

[New advances in inner ear diagnostic imaging].

Recent applications of magnetic resonance in the ear pathology are described. Attention is drawn to the new magnetic resonance sequences in two and three dimensions and their contribution to the understanding of anatomy and pathology of the inner ear, especially the membranous labyrinth.

Ear Neoplasms↗
PubMed1997

No evidence for linkage between leprosy susceptibility and the human natural resistance-associated macrophage protein 1 (NRAMP1) gene in French Polynesia.

In order to determine whether a human homolog (NRAMP1) to a murine candidate gene for resistance to mycobacteria influences susceptibility to human disease, we analyzed data from seven multicase leprosy families (84 individuals) from French Polynesia for linkage markers within the NRAMP1 gene and leprosy per se. Individual family members were typed at nine polymorphic loci within NRAMP1. In addition, three physically linked, polymorphic microsatellite markers-D2S104, D2S173 and D2S1471-were also typed. Linkage analyses were done using affected sibpair and LOD score methods employing different modes of inheritance with full and reduced penetrance. The results of this study strongly suggest that NRAMP1 is not linked to leprosy susceptibility in the French Polynesian families tested.

Alleles↗
PubMed1996

Development of projections from transplants of embryonic medial or lateral frontal cortex placed in the lateral frontal cortex of newborn hosts.

Several recent experiments using neocortical transplantation paradigms indicated that embryonic neurons grafted in a heterotopic locus retain development characteristics corresponding to their site of origin. In the present study, limited portions of lateral (lateral-to-lateral) or medial (medial-to-lateral) sectors of embryonic (E16) frontal cortex were grafted into the lateral frontal cortex of newborn rats. A retrograde tracer was injected 3-4 months later into the dorsomedial or ventrolateral sectors of the host caudate-putamen (CPU). The results indicate that the mediolateral arrangement of striatal projection developed by lateral-to-lateral transplants is virtually identical to that found in intact rats. A very weak proportion of the transplanted cells distribute fibers to the dorsomedial sector of the CPU. In marked contrast, the proportion of efferents from medial-to-lateral transplants projecting to the dorsomedial CPU is by far larger than the one directed to the ventrolateral CPU. Our findings provide evidence that even within one single neocortical area (the frontal neocortex) some degree of prespecification (medial versus lateral patterns of efferent projections) is already present at E16.

Age Factors↗
PubMed1996

Development of spinal cord projections from neocortical transplants heterotopically placed in the neocortex of newborn hosts is highly dependent on the embryonic locus of origin of the graft.

Previous experiments based on heterotopic transplantation paradigms have indicated that the distribution of efferents developed by layer V pyramidal cells seems to be related to where in the neocortex the cells develop and not to where they were generated. The present study was undertaken in an attempt to obtain a quantitative estimation of the weight of extrinsic factors in the development of neocortical efferents. Fragments of embryonic (E15-E19) frontal or occipital cortex were grafted homotopically or heterotopically into the frontal or occipital cortex of newborn rats. As adults, the hosts received an injection of a retrograde tracer into the pyramidal tract decussation, and the distribution of the subsequent cell labeling was examined in each category of transplant. The mean numbers of labeled cells were 725 in frontal-to-frontal transplants and 250 in frontal-to-occipital transplants. In occipital-to-frontal transplants, the numbers of labeled cells were extremely low, ranging from 0 to 14. Finally, as expected, practically no cell labeling was found in occipital-to-occipital transplants. Thus, transplants of presumptive frontal origin systematically develop and maintain in adulthood a spinal cord projection even though they are placed in the host occipital cortex. Conversely, transplants of presumptive occipital origin are practically incapable of maintaining a spinal cord projection in adulthood even though they are placed in the host frontal cortex. It seems, therefore, that the generation of regional differences in efferent connectivity found in the mature cortex depends on early regional specification within the neocortical neuroepithelium.

Animals↗
PubMed1996

Comparison of the serum-supplemented Todd-Hewitt and the new Haemophilus test media for broth microdilution susceptibility testing of Streptococcus pneumoniae.

Horse serum-supplemented Todd-Hewitt broth (STH) in use at Hôpital Ste-Justine for the last 12 years was compared to the recently proposed Haemophilus test medium (HTM), for broth microdilution susceptibility testing of Streptococcus pneumoniae. One hundred and twenty S. pneumoniae isolates from pediatric clinical specimens were used in this study. In general, the minimum inhibitory concentrations (MICs) in STH for 15 antimicrobial agents were quite comparable to those determined in HTM but tended to be higher. Drugs which generated MICs within +/- 1 log2 concentration differences in both media included penicillin, ampicillin, oxacillin, cefuroxime, cefotaxime, cefixime, clindamycin, chloramphenicol, trimethoprim-sulfamethoxazole, rifampin, ciprofloxacin and vancomycin. Cefaclor and tetracycline MICs tended to be > or = 2 log2 dilutions higher with STH for most of the isolates tested, while erythromycin MICs were often 2 log2 dilutions lower with STH than with HTM. Despite some differences in MICs noted above, few very major (0.4%), major (0.2%) and minor interpretive category errors (4.4%) were observed. The visual reading of the MICs for most of the 120 clinical isolates tested was generally easier in STH which was superior in supporting best the bacterial growth as detected by spectrophotometry. The risk of false susceptibility is thus decreased by using STH rather than HTM; furthermore, STH is free of the technical problems of the lysed horse blood Mueller-Hinton (LHB-MH) recommended by the NCCLS.

Animals↗