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C Carron

Publications and source records attributed to C Carron.

9 recordsLinked to original sources
PubMed2001

Cloning and developmental expression of STAT5 in Xenopus laevis.

Transcription factors of the signal transducer and activator of transcription (STAT) family are required for cellular responses to multiple signalling molecules. After ligand binding-induced activation of cognate receptors, STAT proteins are phosphorylated, hetero- or homodimerize, and enter the nucleus. STAT dimers bind to specific DNA elements and alter the transcriptional activity of the signal-responsive genes. We report the cloning and developmental pattern of expression of XSTAT5, a Xenopus laevis member of the STAT family, closely related to the mammalian STAT5A and STAT5B. XSTAT5 is expressed maternally and zygotically. With the onset of neurulation, XSTAT5 RNA are clearly localized in the anterior neural plate and subsequently in the neural structures of the developing eye, the pineal gland and the cement gland anlage. At late tailbud stages, a faint expression is detected in a ventral location that might correspond to the ventral blood islands.

Amino Acid Sequence↗
PubMed2000

TEL-JAK2 transgenic mice develop T-cell leukemia.

We previously reported a fusion between TEL and JAK2 in a t(9;12)(p24;p13) chromosomal translocation in childhood acute T-cell leukemia. This fusion gene encodes a TEL-JAK2 chimeric protein in which the 336 amino-terminal residues of TEL, including its specific self-association domain, are fused to the kinase domain of JAK2. TEL-JAK2 exhibits constitutive activation of its tyrosine kinase activity which, in turn, confers growth factor-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line. To elucidate the properties of TEL-JAK2 in primary cells and to create an animal model for TEL-JAK2-induced leukemia, we generated transgenic mice in which the TEL-JAK2 complementary DNA was placed under the transcriptional control of the EmuSRalpha enhancer/promoter. TEL-JAK2 founder mice and their transgenic progeny developed fatal leukemia at 4 to 22 weeks of age. Selective amplification of CD8-positive T cells was observed in blood, lymph nodes, thymus, spleen, and bone marrow. Expression of a tyrosine-phosphorylated TEL-JAK2 protein and activation of STAT1 and STAT5 (signal transducer and activator of transcription) were detected in leukemic tissues. TEL-JAK2 diseased mice also displayed invasion of nonhematopoietic organs, including liver, brain, lung, and kidney, by leukemic T cells. Leukemic organs of founder and transgenic progeny contained a monoclonal/oligoclonal T-cell population as analyzed by the rearrangement of the TCRbeta locus. Transplantation of TEL-JAK2 leukemic cells in nude mice confirmed their invasive nature. We conclude that the TEL-JAK2 fusion is an oncogene in vivo and that its expression in lymphoid cells results in the preferential expansion of CD8-positive T cells. (Blood. 2000;95:3891-3899)

Animals↗
PubMed2000

Intermittent infusion of inotropes in the outpatient setting: one-year post treatment analysis.

The course of patients with New York Heart Association (NYHA) class III and IV and refractory heart failure symptoms is characterized by progressive clinical deterioration and frequent hospital readmissions. The value of intermittent intravenous administration of inotropes in managing this group of patients in the outpatient setting has been controversial. In this study, patients with refractory heart failure symptoms were enrolled to assess the impact of a multidisciplinary outpatient program in terms of on hospital admissions, emergency room visits, and interval free of symptoms after administration of inotropes. This is a retrospective analysis on 41 patients with refractory heart failure treated at our outpatient cardiac infusion unit over a 20 month period. Thirteen patients with a NYHA class III [age 64 +/- 13; LVEF 27 +/- 9%] and 28 patients with a NYHA class IV [age 65 +/- 13 years; LVEF 21 +/- 9%], mostly males, were included. A total of 65 admissions for decompensated HF were recorded in the previous 6-months prior to initiation of the outpatient program; compared to only 4 emergency room visits and 7 hospital admissions after enrollment. Furthermore, 17 patients have been discharged with improvement in NYHA class from 3.5 +/- 0.6 to 1.4 +/- 0.5. On these patients, the interval free of symptoms since the last infusion treatment has ranged from 201 to 489 days, without emergency room visits or hospital admissions for congestive heart failure. The results of this study support the use of intermittent infusion of inotropes in the outpatient setting. Although the natural history for patients with refractory heart failure has been grim; the use of these intermittent infusions may in fact alter the natural course of end stage congestive heart failure patients and deserves further investigation.

Adult↗
PubMed1999

TEL is a sequence-specific transcriptional repressor.

TEL is a gene frequently involved in specific chromosomal translocations in human leukemia and sarcoma that encodes a member of the ETS family of transcriptional regulators. TEL is unusual among other ETS proteins by its ability to self-associate in vivo, a property that is essential to the oncogenic activation of TEL-derived fusion proteins. We show here that TEL is a sequence-specific transcriptional repressor of ETS-binding site-driven transcription of model and natural promoters. Deletion of the oligomerization domain of TEL or its substitution by the homologous region of monomeric ETS1 impaired the ability of TEL to repress. In contrast, substitution of the oligomerization domain of TEL by unrelated oligomerization domains resulted in an active repressor, showing that the ability of TEL to repress depends on its ability to self-associate. The study of the properties of TEL fusions to the heterologous DNA binding domain of Gal4 identified two autonomous repression domains in TEL, distinct from its oligomerization domain, that are essential to the ability of TEL to repress ETS-binding site-containing promoters. These results have implications for the normal function of TEL, its relation to other ETS proteins, and its role in leukemogenesis.

Animals↗
PubMed1997

The TEL gene products: nuclear phosphoproteins with DNA binding properties.

The human TEL gene is involved in several 12p13 chromosomal abnormalities present in various human hematological malignancies, the most frequent being the t(12;21)(p13;q22), specific for childhood acute lymphoblastic leukemia. The predicted product of TEL harbours an amino acid region similar to the ETS DNA binding domain. We now report the isolation of the murine TEL cDNA and the characterization of the human TEL proteins. Human and murine TEL proteins are particularly homologous within their aminoterminal regions and their ETS domains. TEL proteins are nuclear and display specific DNA binding activity toward classical ETS binding sites. In addition, we show that TEL mRNAs initiate translation at either of the two first inframe ATGs (codon 1 and 43) to encode 50 kDa and 57 kDa TEL proteins. In vivo, each of these primary translational products is modified by multiple phosphorylation events.

Animals↗
PubMed1997

A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFR beta oncoprotein.

TEL is a novel member of the ETS family of transcriptional regulators which is frequently involved in human leukemias as the result of specific chromosomal translocations. We show here by co-immunoprecipitation and GST chromatography analyses that TEL and TEL-derived fusion proteins form homotypic oligomers in vitro and in vivo. Deletion mutagenesis identifies the TEL oligomerization domain as a 65 amino acid region which is conserved in a subset of the ETS proteins including ETS-1, ETS-2, FLI-1, ERG-2 and GABP alpha in vertebrates and PNTP2, YAN and ELG in Drosophila. TEL-induced oligomerization is shown to be essential for the constitutive activation of the protein kinase activity and mitogenic properties of TEL-platelet derived growth factor receptor beta (PDGFR beta), a fusion oncoprotein characteristic of the leukemic cells of chronic myelomonocytic leukemia harboring a t(5;12) chromosomal translocation. Swapping experiments in which the TEL oligomerization domain was exchanged by the homologous domains of representative vertebrate ETS proteins including ETS-1, ERG-2 and GABP alpha show that oligomerization is a specific property of the TEL amino-terminal conserved domain. These results indicate that the amino-terminal domain conserved in a subset of the ETS proteins has evolved to generate a specialized protein-protein interaction interface which is likely to be an important determinant of their specificity as transcriptional regulators.

Amino Acid Sequence↗
PubMedDate not supplied

Outpatient cardiac infusion units: impact in elderly patients with refractory heart failure.

BACKGROUND: The use of intermittent intravenous infusions of inotropic drugs is under evaluation in the management of patients with refractory heart failure. OBJECTIVES: We investigated the impact of intermittent outpatient infusions of inotropes on hospital admissions, emergency room visits, functional class, and symptom-free interval after administration of inotropes to elderly patients with advanced heart failure symptoms. METHODS: This retrospective analysis involved 24 elderly outpatients with a New York Heart Association class of III or IV and refractory heart failure symptoms. RESULTS: Seven patients with class III heart failure (age 74A+/-4 years; left ventricular ejection fraction 27A+/-9%) and 17 patients of class IV (age 73A+/-4 years; LVEF 21A+/-10%) were included. Twenty patients were males. A total of 365 outpatient treatment sessions were administered, with 15A+/-9 sessions per patient (range, 6-43). Eleven patients improved and were discharged; seven patients died; three discontinued treatment; two patients remain on therapy; and one patient required continuous infusion. During this treatment, there were only three emergency room visits and six hospital admissions due solely to heart failure. Fourteen patients required no emergency room visits or hospitalization. Of the patients discharged from the program, the interval without heart failure symptoms ranged from 60-356 days, with an improvement in NYHA class from 3.5A+/-0.6 to 1.4A+/-0.5 and no emergency room visits or hospital admissions. CONCLUSIONS: This type of therapy is well tolerated among elderly patients with refractory heart failure symptoms and its use deserves further investigation.

Aged↗