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M J Lecomte

Publications and source records attributed to M J Lecomte.

10 recordsLinked to original sources
PubMed1999

Murine Stat2 is uncharacteristically divergent.

Characterization of the ability of human interferons (IFNs) to rapidly induce genes led to the identification of the first two members of the STAT (signal transducers and activators of transcription) family, Stat1 and Stat2. To study the unique role of this transcription factor in IFN signaling under more physiological conditions, murine Stat2 was isolated and found to be surprisingly divergent. This divergence was most striking in the C-terminal transcriptional activation domain. Studies on murine Stat2 indicate that it functions in IFN signaling. This includes IFN-alpha-dependent activation, nuclear translocation, DNA binding and activation of reporter genes. However, the profound divergence at the C-terminus suggests that murine Stat2 may have evolved to mediate some unique functions as well. To explore this possibility, proteins that interact with the C-termini of murine and human Stat2 were examined. These studies indicate that the murine and human C-termini interact with an overlapping, but distinct set of proteins.

Amino Acid Motifs↗
PubMed1999

Involvement of intronic sequences in cell-specific expression of the peripherin gene.

Peripherin is an intermediate filament protein expressed in restricted populations of neurons. Our previous study of the chromatin structure of the mouse peripherin gene in cells that do or do not express peripherin suggested that the region located between -1,500 and +800 bp of the gene could be involved in its cell specificity. In the present work, we performed an in vitro functional analysis of the 5' flanking region of the mouse peripherin gene and observed that this region up to 9 kb contained both enhancer and inhibiting activities; however, it was insufficient to achieve a complete extinction of reporter gene expression in peripherin-negative cells. Furthermore, analysis of the first three introns with the 5' flanking sequences of the gene showed that intron I greatly increased specificity of the gene expression. Intron I also conferred the same properties to thymidine kinase heterologous promoter. DNase I footprinting experiments performed with intron I revealed at least two protected regions (Inl A and Inl B). Inl A encompasses an AP-2-like binding site that interacted with both neuroblast and fibroblast nuclear factors, as well as with the recombinant AP-2alpha protein. However, gel shift experiments suggested that the interacting nuclear factors are distinct from AP-2alpha itself and probably belong to the AP-2 family. Inl B perfectly matched the consensus binding site for Sp1 and specifically interacted with nuclear protein factors that showed the same binding properties as the Sp1 family members. Fine deletion analysis of intron I indicated that the Inl A element alone is responsible for its enhancing properties, whereas a region located between +789 and +832 gives to intron I its silencer activity.

3T3 Cells↗
PubMed1998

Transcriptional activation of the mouse peripherin gene by leukemia inhibitory factor: involvement of STAT proteins.

Peripherin is a neuron-specific intermediate filament protein whose expression is activated in vitro by the neuropoietic cytokines leukemia inhibitory factor (LIF) and interleukin-6. We have studied the mechanisms of transcriptional activation of the peripherin gene by LIF. In particular, we have identified a 70-bp element [peripherin cytokine-responsive element (Pe-CyRE)] within the 5'-flanking sequences of the mouse peripherin gene (between -930 and -860) that enhances transcription in two neuroblastoma cell lines, NBFL and LA-N-2, in response to LIF treatment. We have also shown by DNA mobility shift assays that treatment of cells by LIF induces the binding of protein complexes composed of at least two members of the signal transducers and activators of transcription (STAT) factor family to a cis element (Pe-APRE2) within Pe-CyRE. Furthermore, the entire Pe-CyRE, as well as Pe-APRE2, conferred responsiveness onto a heterologous thymidine kinase promoter. However, the response amplitude of the heterologous promoter to LIF was lower than that observed with the 5'-flanking sequences of the peripherin promoter, suggesting that cooperative interactions with surrounding sequences of the peripherin gene are required for a full transcriptional activation.

Acute-Phase Proteins↗
PubMed1998

[Prostatic localization revealing an acute myeloid leukemia. Apropos of a case].

The authors report an original case of acute myeloid leukaemia (AML) presenting in the form of acute urinary retention, confirmed by prostatic biopsy, with complete absence of any non-urological clinical features. Prostatic sites of leukaemia are frequent and classically reported, but often occur during the course of known leukaemia, and are rarely symptomatic, justifying biopsies in the presence of any prostatic symptoms. Immunolabelling represents the key to the diagnosis in the presence of undifferentiated cells demonstrated on prostatic biopsies. The outcome was fatal in this case, despite early chemotherapy. The clinical features, clinical course and therapeutic aspects of prostatic leukaemia are discussed.

Acute Disease↗
PubMed1996

Three different states of the chromatin structure of the mouse peripherin gene.

The chromatin structure of the mouse peripherin gene domain was analyzed in peripherin-positive and -negative cell lines. At least nine DNase I hypersensitive sites (HSS) are present within the 20-kb peripherin domain in the mouse neuroblastoma cell lines which express peripherin. Three of them are situated in intron I and intron III, the others being distributed within the 5' flanking region up to -5.5 kb. The presence of these sites was also investigated in the peripherin chromatin domain of peripherin-negative cell lines. Two other types of HSS distribution were observed along the peripherin gene according to the category of cell considered: constantly peripherin-negative cells, or negative cells arising from transiently peripherin-expressing precursors. From comparison of HSS patterns in these cell lines with those of neuroblastoma cells, it can be predicted that HSS located in the region -1500/+800 bp participate in cell-specific expression of the mouse peripherin gene.

3T3 Cells↗
PubMed1979

[Hemoglobin A1c and diabetes control (author's transl)].

Hemoglobin A1c (HbA1c) is a minor component of human hemoglobin resulting from a non enzymatic linkage of glucose with the NH2-terminal amino acid of the beta chain of hemoglobin. Under normal conditions, HbA1c represent about 5% of total hemoglobin. The HbA1c blood concentration increases in direct proportion of the duration and degree of hyperglycemia. Available procedures for measuring HbA1c include column chromatography, high pressure liquid chromatography, a colorimetric procedure based on the formation of 5-hydroxymethylfurfural and isoelectrofocusing. In a group of 138 patients, we have confirmed that HbA1c provides a useful means of evaluating the degree of diabetic control: the highest values have been recorded in cases of poor control, the lowest in cases of excellent control. In the latter case, the HbA1c values recorded were not statistically different from those obtained in a control group of 92 non-diabetic subjects. The interest of evaluating this parameter in diabetes is briefly analyzed.

Adult↗
PubMed1976

Studies on the pathogenesis of reactive hypoglycemia: role of insulin and glucagon.

Fifty-eight patients with biochemical reactive hypoglycemia (blood glucose 45 mg% or less after a 100 g OGTT) were tested, of whom 11 subjects were obese with normal glucose tolerance, 9 were obese with chemical diabetes, 9 had chemical diabetes without obesity, 6 had undergone gastrectomy, 7 had renal glycosuria and 16 were apparently isolated. An exaggerated insulin response to oral glucose was associated with reactive hypoglycemia in the post-gastrectomy syndrome, in normal-weight patients with chemical diabetes and 44% of the patients with the isolated syndrome. In contrast, plasma-insulin values cannot account for the reactive hypoglycemia observed in obese patients (with or without chemical diabetes), in subjects with renal glycosuira and in 56% of the patients with the isolated syndrome. A study of pancreatic-glucagon secretion in a group of twelve subjects with "isolated normoinsulinemic reactive hypoglycemia" failed to demonstrate any significant abnormality in the secretion of this hormone during oral glucose tolerance test or intravenous insulin tolerance test. As suggested by Permutt et al. (1973) biguanide therapy may be useful in the treatment of patients presenting severe and symptomatic reactive hypoglycemia which does not respond to classical dietary management.

Blood Glucose↗