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L Cossette

Publications and source records attributed to L Cossette.

10 recordsLinked to original sources
PubMed2003

Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions.

Myotonic dystrophy (DM1) is caused by the expansion of a trinucleotide repeat (CTG) located in the 3'untranslated region of the myotonic dystrophy protein kinase gene, for which currently there is no effective treatment. The data available suggest that misregulation of RNA homeostasis may play a major role in DM1 muscle pathogenesis. This indicates that the specific targeting of the mutant DMPK transcripts is essential to raise the rationale basis for the development of a specific gene therapy for DM1. We have produced a retrovirus which expresses a 149-bp antisense RNA complementary to the (CUG)13 repeats and to the 110-bp region following the repeats sequence to increase the specificity. This construct was introduced into human DM1 myoblasts, resulting in a preferential decrease in mutant DMPK transcripts, and effective restoration of human DM1 myoblast functions such as myoblast fusion and the uptake of glucose. It was previously shown that delay of muscle differentiation and insulin resistance in DM1 are associated with misregulation of CUGBP1 protein levels. The analysis of CUGBP1 levels and activity in DM1 cells expressing the antisense RNA indicated a correction of CUGBP1 expression in infected DM1 cells. We therefore show that current antisense RNA delivered in vitro using a retrovirus is not only capable of inhibiting mutant DMPK transcripts, but also can ameliorate dystrophic muscle pathology at the cellular levels.

Blotting, Northern↗
PubMed2001

A founder mutation in French-Canadian families with X-linked hereditary neuropathy.

BACKGROUND: The aim of the present study was to identify the mutations in the connexin 32 gene in French-Canadian families with X-linked Charcot-Marie-Tooth disease (CMTX). METHODS: Molecular analysis was performed by nonisotopic single strand conformation polymorphism (SSCP) analysis and sequencing. Clinical evaluation was carried out according to the scale defined by the European Hereditary Motor and Sensory Neuropathy Consortium. RESULTS: In one family, the mutation Arg142Trp was located in the transmembrane domain III whereas, in four other families we identified a novel mutation (Ser26Trp) located in the transmembrane domain I of the connexin 32 gene. Haplotype analysis revealed that these four families are related and suggests a founder mutation. Sixteen patients from these four families were studied. As expected, all the affected males were more clinically affected than the females and all affected patients exhibited some electrophysiological characteristics of demyelination. CONCLUSION: Our study suggests that the Ser26Trp mutation may cause a primary demyelinating neuropathy that is not associated with a specific clinical phenotype. We also find evidence that the majority of kindreds share a common ancestor.

Adult↗
PubMed1999

Clinical and electrophysiological study in French-Canadian population with Charcot-Marie-tooth disease type 1A associated with 17p11.2 duplication.

BACKGROUND: The aim of the present study was to examine the frequency and the phenotypic manifestations in a French-Canadian population with a chromosome 17p11.2 duplication (Charcot-Marie-Tooth type 1A, CMT-1A). METHODS: Molecular analysis were performed by Southern blot using pVAW409R3a probe. Clinical evaluation was carried out according to the scale defined by the European HMSN Consortium. RESULTS: The frequency of duplication was found to be similar in the adult (70.8%) and pediatric (72.7%) populations. Onset of symptoms occurred before 20 years of age in 85.7% of adult cases and before the age of 5 in 80% of the pediatric cases. The classical CMT syndrome was observed in 77% of the cases and the syndrome was associated with additional features in 15% of cases in the adult population. All the children presented with classical CMT syndrome with no additional features. There was a significant correlation between the disability score and the duration of the disease but no correlation was found between median nerve conduction velocity and the functional handicap, the age at onset or the duration of the disease. In one family, there was a very conspicuous anticipation over five observed generations. CONCLUSION: This study reveals that the age at onset, the clinical and electrophysiological variability as well as the functional disability variations in a French-Canadian population did not differ from those reported in other populations.

Adolescent↗
PubMed1994

Red blood cell Cu/Zn superoxide dismutase activity in sporadic amyotrophic lateral sclerosis.

To determine the possible role of Cu/Zn superoxide dismutase (SOD1) in the pathophysiology of sporadic amyotrophic lateral sclerosis (SALS), we measured SOD1 activity in red blood cell lysates in patients with SALS. SOD1 activity in red blood cell lysates was independent of age and sex in control patients, and no significant difference was found between the levels of SOD1 activity in controls (1174.8 +/- 213, n = 29) and SALS patients (1203.4 +/- 214, n = 27). These results suggest that point mutations in the SOD1 gene are apparently unrelated to SALS.

Adult↗
PubMed1994

Interleukin-12 induces tyrosine phosphorylation and activation of 44-kD mitogen-activated protein kinase in human T cells.

Interleukin-12 (IL-12) is a novel cytokine that enhances numerous functional activities of human T cells and natural killer (NK) cells. The present studies were undertaken to characterize some of the early signaling events following IL-12 stimulation of mitogen-activated normal T cells. In these cells, IL-12 induces rapid tyrosine phosphorylation of proteins of 21, 44, and 54 kD. However, IL-12 does not induce tyrosine phosphorylation in normal resting T cells. In conjunction with increased tyrosine phosphorylation of several substrates, IL-12 stimulation resulted in increased in vitro kinase activity of immunoprecipitated tyrosine phosphorylated proteins. The 44-kD protein has been characterized as one isoform of the mitogen-activated protein (MAP) kinase family. Increased tyrosine phosphorylation of MAP kinase following IL-12 stimulation was also associated with enhanced enzymatic activity of this protein in vitro as measured by myelin basic protein phosphotransferase assay. These studies identify MAP kinase as one of the intracellular elements of the IL-12 signaling pathway in human T cells.

Enzyme Activation↗
PubMed1991

[Post natal depression: the socio-environmental factors].

In the weeks and months that follow the birth of a child, between 10 and 20 per cent of mothers experience serious or moderate symptoms of depression. This state of psychological distress affects the mother-infant interaction, and can modify the child's development in the longer term. Recent studies increasingly link these symptoms to environmental and psychosocial stress factors. The setting up of relevant and efficient prevention and promotion programs requires a better understanding of the effect of stress and social support on the mental health of mothers.

Child Development↗
PubMed1990

[Masculine inexpressiveness: myths and facts].

This article examines the common admission that men express their emotions less than do women. Research data shows little difference between the behaviours of boys and girls before adolescence. During adulthood, however, evidence points to men being less expressive than women except in situations involving aggressive behaviour. Men's diminished expressiveness is apparent in a context of intimate interaction. But in situations where they compete for social status, men seem more likely to express emotions. The authors suggest that more studies take into account the social contexts of emotional expressiveness generated by division of labor based on sex.

Adolescent↗