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L Nicole

Publications and source records attributed to L Nicole.

At least 19 recordsLinked to original sources
PubMed2005

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families.

The goal of this study was to identify susceptibility loci shared by schizophrenia (SZ) and bipolar disorder (BP), or specific to each. To this end, we performed a dense genome scan in a first sample of 21 multigenerational families of Eastern Quebec affected by SZ, BP or both (N=480 family members). This probably constitutes the first genome scan of SZ and BP that used the same ascertainment, statistical and molecular methods for the concurrent study of the two disorders. We genotyped 607 microsatellite markers of which 350 were spaced by 10 cM and 257 others were follow-up markers in positive regions at the 10 cM scan. Lander and Kruglyak thresholds were conservatively adjusted for multiple testings. We maximized the lod scores (mod score) over eight combinations (2 phenotype severity levels x 2 models of transmission x 2 analyses, affected/unaffected vs affected-only). We observed five genomewide significant linkages with mod score >4.0: three for BP (15q11.1, 16p12.3, 18q12-q21) and two for the shared phenotype, that is, the common locus (CL) phenotype (15q26,18q12-q21). Nine mod scores exceeded the suggestive threshold of 2.6: three for BP (3q21, 10p13, 12q23), three for SZ (6p22, 13q13, 18q21) and three for the CL phenotype (2q12.3, 13q14, 16p13). Mod scores >1.9 might represent confirmatory linkages of formerly reported genomewide significant findings such as our finding in 6p22.3 for SZ. Several regions appeared to be shared by SZ and BP. One linkage signal (15q26) appeared novel, whereas others overlapped formerly reported susceptibility regions. Despite the methodological limitations we raised, our data support the following trends: (i) results from several genome scans of SZ and BP in different populations tend to converge in specific genomic regions and (ii) some of these susceptibility regions may be shared by SZ and BP, whereas others may be specific to each. The present results support the relevance of investigating concurrently SZ and BP within the same study and have implications for the modelling of genetic effects.

Adult↗
PubMed2004

Inclusion of ibuprofen in mesoporous templated silica: drug loading and release property.

The aim of this study is to determine the feasibility of loading biologically active molecules into templated mesoporous silica (MCM 41). This material shows an important mesoporosity associated to hexagonally organized channels, a narrow pore size distribution and a large surface area. Ibuprofen was selected as a model molecule since it is a well documented and much used anti-inflammatory drug. Furthermore, it has a lipophilic character and its molecular size is suitable for inclusion within the mesopores of the MCM 41 material. In order to load ibuprofen within the mesopores, adsorption experiments using various solvents or successive impregnations with solutions of ibuprofen in ethanol were performed. At each step of the loading process, the pore filling was characterized by nitrogen adsorption experiments and by X-ray diffraction. The impregnation procedure results in a significant improvement of the amount of ibuprofen loaded into MCM 41. The in vitro drug release was investigated with simulated biological fluids (gastric and intestinal). Hundred percent release is observed at the end of the in vitro experiment.

Drug Carriers↗
PubMed2001

A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes.

We report the first stage of a genome scan of schizophrenia (SZ) and bipolar disorder (BP) covering 18 candidate chromosomal areas. In addition to testing susceptibility loci that are specific to each disorder, we tested the hypothesis that some susceptibility loci might be common to both disorders. A total of 480 individuals from 21 multigenerational pedigrees of Eastern Québec were evaluated by means of a consensus best-estimate diagnosis made blind to diagnoses in relatives and were genotyped with 220 microsatellite markers. Two-point and multipoint model-based linkage analyses were performed and mod scores (Z, for max Z(max)) are reported. The strongest linkage signals were detected at D18S1145 (in 18q12; Z = 4.03) for BP, and at D6S334 (in 6p 22-24; Z(het) = 3.47; alpha = 0.66) for SZ. Three other chromosomal areas (3q, 10p, and 21q) yielded linkage signals. Chromosomes 3p, 4p, 5p, 5q, 6q, 8p, 9q, 11q, 11p, 12q, 13q, 18p and 22q showed no evidence of linkage. The 18q12 results met the Lander and Kruglyak (1995) criterion for a genome-wide significant linkage and suggested that this susceptibility region may be shared by SZ and BP. The 6p finding provided confirmatory evidence of linkage for SZ. Our results suggest that both specific and common susceptibility loci must be searched for SZ and BP.

Adult↗
PubMed2001

[Schizophrenia and cognitive behavioral psychotherapy].

OBJECTIVE: To distinguish between different approaches of cognitive-behavioural therapy (CBT) for schizophrenia depending on the goals, objectives and methods of these approaches, then to discuss efficacy studies. METHOD: A summary of information collected through electronic (MEDLINE, PSYchlit) and bibliographic research. RESULTS: CBTs all broadly attempt to bring a better cognitive, behavioural and emotional adjustment to the psychotic experience by suggesting to the patient a new explanatory model of psychosis: the vulnerability-stress model. These approaches involve different levels and goals. Some focus on correcting basic cognitive deficits or modifying the psychotic symptoms and the related distress. At the other end of the spectrum, metacognitive therapies aim to modify and restructure dysfunctional self and environment schemas to enable the development of better-adjusted and generally applied cognitive strategies. A few studies with limited power and methods have shown the efficiency of those therapies. CONCLUSION: CBTs prove to be a promising additive treatment. They have been shown to improve social adjustment and quality of life, and to diminish psychotic symptoms and the related distress. They address all positive, negative, cognitive, behavioural, and emotional symptoms while considering the stage of the disease and the patient's special needs. Further research is needed to establish the duration, the best provision frequency, and the specificity of these approaches.

Cognitive Behavioral Therapy↗
PubMed1997

6p24-22 region and major psychoses in the Eastern Quebec population. Le Groupe IREP.

Recent reports of a linkage trend in 6p24-22 for schizophrenia (SZ), in different samples, were tempered by the concurrent evidence of negative reports in other samples. In the studies showing positive results, different definitions of affection and a wide spectrum of diagnoses were used. Our objectives were not only to test for linkage at 6p24-22 in the Eastern Quebec population, but also to test whether this putative vulnerability locus was either selectively linked to schizophrenia (SZ), or to bipolar disorder (BP), or to both major psychoses. Parametric and nonparametric linkage analyses with 12 microsatellite markers in 6p24-p22 were performed on a sample of 18 large multigenerational pedigrees (N = 354) either affected by SZ, or by BP, or equally affected by both major psychoses (i.e., mixed pedigrees). Three affection definitions were usually tested in our program: one on schizophrenia (SZ), one on bipolar disorder (BP), and one that comprised SZ and BP under the hypothesis of a susceptibility locus common to both in major psychoses (common locus, CL). The results of parametric analyses did not support a major gene hypothesis. However, in one large mixed pedigree (#151), we observed with the common locus phenotype (CL) lod scores of 2.49 and 2.15, respectively, at the D6S296 and D6S277 loci under a dominant model. Our data suggest the presence of a potential vulnerability locus at 6p24-22 that could be related to both schizophrenia and bipolar affective disorder. These results may be seen as congruent with former studies that used schizoaffective as well as schizophrenia diagnoses as entry criteria for the affected families, and used an affection definition that comprised affective psychoses as well as schizophrenia.

Bipolar Disorder↗
PubMed1997

Preliminary studies on the relationship between autoantibodies to heat stress proteins and heat injury of pilots during acute heat stress.

Comparison in the heart rate, oral temperature and lymphocyte DNA damage during heat stress was made in pilots with negative antibodies to heat stress proteins (HSPs) and those with positive antibodies in the man-made climate room with Western blot and comet assay. Our results showed that the increase in oral temperature, heart rate and lymphocyte DNA damage in pilots with the positive antibodies to HSPs were higher than those in pilots with the negative antibodies during heat stress. These results indicated that the presence of autoantibodies in plasma of pilots might reflect heat damage and high sensitivity to heat.

Adult↗
PubMed1997

Clinical and methodological factors related to reliability of the best-estimate diagnostic procedure.

OBJECTIVE: The reliability and accuracy of the best-estimate diagnostic procedure were examined, and factors associated with reliability were determined. METHOD: The subjects were 134 members of large multigenerational pedigrees densely affected by bipolar disorders or schizophrenia. Three best-estimate diagnoses were derived: first, by a research psychiatrist and research assistant unblind to the relatives' diagnoses; second, by two blind independent psychiatrists; third, by a panel of four blind psychiatrists. The subjects were characterized on several clinical and methodological variables, which were used to compare the agreements of two types of best-estimate diagnoses with the disagreements. RESULTS: There was satisfactory agreement between the unblind and blind consensus best-estimate diagnoses and between the two blind independent psychiatrists. Latent class analyses revealed that limited sensitivity was the main source of imperfect reliability. Confusability analyses revealed that the most problematic diagnostic distinctions involved schizoaffective disorder, which was confused with schizophrenia, bipolar I disorder, and schizophreniform disorder. Blindness significantly affected diagnostic outcome in latent class analyses. Moreover, for diagnostic disagreements, unblind diagnoses had greater continuity with the most predominant diagnosis in the pedigree than did blind diagnoses. Diagnostic disagreements were associated with the presence of mixed affective and psychotic symptoms, less diagnostic certainty, and shorter duration of illness. CONCLUSIONS: These results suggest that it is possible to identify cases that are more likely to lead to diagnostic disagreements in family and epidemiological studies and that blind diagnoses may help to prevent false positive diagnoses, which may be particularly detrimental to genetic linkage analyses.

Adult↗
PubMed1995

Linkage results on 11Q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia.

The 11q21-22 region is of interest for schizophrenia because several candidate genes are located in this section of the genome. The 11q21-22 region, including DRD2, was surveyed by linkage analysis in a sample (N = 242) made of four large multigenerational pedigrees densely affected by schizophrenia (SZ) and eight others by bipolar disorder (BP). These pedigrees were ascertained in a large area of Eastern Quebec and Northern New Brunswick and are still being extended. Family members were administered a "consensus best-estimate diagnosis procedure" (DSM-III-R criteria) blind to probands and relatives' diagnosis and to pedigree assignment (SZ or BP). For linkage analysis, 11 microsatellite polymorphism (CA repeat) markers, located at 11q21-22, and comprising DRD2, were genotyped. Results show no evidence of a major gene for schizophrenia. However, a maximum lod score of 3.41 at the D11S35 locus was observed in an affected-only analysis of one large SZ family, pedigree 255. Whether or not the positive linkage trend in pedigree 255 reflects a true linkage for a small proportion of SZ needs to be confirmed through the extension of this kindred and through replication.

Base Sequence↗
PubMed1995

Negative, psychoticism, and disorganized dimensions in patients with familial schizophrenia or bipolar disorder: continuity and discontinuity between the major psychoses.

OBJECTIVE: This study aimed to answer the following questions: 1) Can we reliably measure the psychopathologic dimensions of schizophrenia by using a lifetime frame and by rating acute and interepisode periods separately? 2) Can we reproduce in subjects with familial schizophrenia the characteristic three-factor structure of schizophrenic symptoms that has been found previously in general groups of schizophrenic patients? 3) Is the factor structure also present in familial bipolar disorder? METHOD: Lifetime measures of psychotic symptoms were taken through a slightly modified version of the Comprehensive Assessment of Symptoms and History for 138 patients with highly familial DSM-III-R schizophrenia (N = 51), bipolar disorder (N = 44), or spectrum disorders (N = 43). Symptoms were rated separately in the acute episodes and in the stabilized interepisode intervals across the patients' lives. RESULTS: A satisfactory level of reliability was obtained. In this highly familial study group, the positive/negative factorial distinction was replicated, as was a three-factor model similar to that observed in prior general groups of schizophrenic patients. These factors were also present in bipolar affective disorder. The negative, psychoticism, and disorganized factor model applied more to the acute phase of illness than to the stabilized state. CONCLUSIONS: These findings offer an empirical basis for testing biological or genetic variables in relation to negative/positive symptom dimensions, rather than diagnoses. Observations of a shared structure for schizophrenia and bipolar disorder suggest some continuity in the causes of these disorders.

Acute Disease↗
PubMed1992

Lower incidence and increased male:female ratio in schizophrenia.

Patients with an ICD-9 diagnosis of psychotic disorder were assessed for DSM-III-R schizophrenia. Rates of schizophrenia were found to be higher in males (39.8 per 100,000) than females (22.4 per 100,000). The DSM-III-R incidence supports recent studies which suggest a decrease in rates of schizophrenia across time, and also suggests that men suffer from both more schizophrenia and a more severe form of the disease.

Adult↗
PubMed1980

[Regulation of genetic expression during the transfer of information from the nucleus to the cytoplasm].

In eukaryotes, the transfer of genetic information from the genome to its final site of phenotypic expression is a multistep process. These steps are described and the mechanisms of regulation operating at these various levels are reviewed. The heat shock response in two diptera, Drosophila and Chironomus, is described as a model system to illustrate the existence of regulation mechanisms at different levels of genetic information transfer. In Chironomus tentans like in Drosophila, a short heat shock (10 min, 39 degrees C) treatment induces the synthesis of at least 8 new proteins. This is accompanied by a drastic reduction in the synthesis of the normal proteins that in those synthesized prior to the shock. The localisation of these induced proteins has been studied by microdissection of the various intranuclear and intracellular compartments of salivary glands. While most of these have a ubiquitous distribution, one induced protein (34 000 Daltons) is exclusively localized in the nucleus. Another one (25 000 Daltons) is mainly concentrated in a particulate form which cosediments with ribosomes. Arsenite and anaerobiosis do not induce a heat shock mimicking response in Chironomus. The induction mechanisms as well as the transcriptional and translational controls operating during the heat shock response are discussed.

Animals↗
PubMed1979

Ribosomes of Physarum polycephalum. Subunits and protein composition.

Ribosomes from Physarum polycephalum were purified. Optimal conditions for preparation and stability of subunits were determined. KCl concentration above 200 mM induced protein dissociation from the subunits. It was observed that dissociated ribosomes were more stable in a low ionic strength buffer than in 200 mM KCl, where the 40 S was preferentially degraded by ribonucleases. Ribosomal proteins were analyzed by two-dimensional gel electrophoresis. The first dimension was carried out at pH 8.6 while the second was run at pH 4.6. The monosome contained sixty seven proteins, of which six were acidic. Two proteins were lost after subunit dissociation. Twenty six basic and two acidic proteins were observed in the 40 S subunit while the largest subunit gave thirty nine spots on the basic part of the gel and three additional spots on the acidic side. Five proteins were shared by 40 S and 60 S.

Electrophoresis, Polyacrylamide Gel↗
PubMed1977

Ultrastructural and radioautographic investigation of the nucleolar cycle in Physarum polycephalum. Characterization of DNA-containing subunits.

The present study has been mainly focused on the nucleolar cycle in the slime mould Physarum polycephalum. The ultrastructural characteristics of the interphase nucleolus, in this species, are quite similar to those of nucleoli in other organisms: it is essentially constituted of large particulate zones surrounding denser regions which are predominantly fibrillar in texture. The latter nucleolar zones, following fixation with osmium tetroxide, are characterized by the presence of opaque granules approximately 25 nm in diameter. Contrary to the situation which generally prevails in other eukaryotes, the late prophase nucleolus fragments into numerous globular bodies which are recognizable by the presence of opaque particles. These fibrillogranular nucleolar fragments persist during mitosis and are observed to become incorporated in the newly formed nucleolus. High-resolution radioautographic observations reveal that these nucleolar remnants contain DNA. The present observations together with recent biochemical data from other authors on the characteristics and mode of duplication of nucleolar DNA in P. polycephalum have led us to the hypothesis that the nucleolus, in this organism, contains several distinct globular subunits each containing ribosomal DNA as a key component. The existence of such morphological subunits appears to account for the unusual behaviour of the nucleolus during the cell cycle.

Autoradiography↗