Biomedical subjects

J Cools

Publications and source records attributed to J Cools.

24 records · Page 2Linked to original sources

PubMed1999

Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13).

The ETV6 gene (also known as TEL) is the main target of chromosomal translocations affecting chromosome band 12p13. The rearrangements fuse ETV6 to a wide variety of partner genes in both myeloid and lymphoid malignancies. We report here 4 new cases of acute myeloid leukemia (AML) with very immature myeloblasts (French-American-British [FAB]-M0) and with a t(4;12)(q11-q12;p13). In all cases, ETV6 was found recombined to a new gene, homologous to the mouse Brx gene. The gene was named BTL (Brx-like Translocated in Leukemia). Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments indicate that the expression of the BTL-ETV6 transcript, but not of the reciprocal ETV6-BTL transcript, is a common finding in these leukemias. In contrast to the majority of other ETV6 fusions, both the complete helix-loop-helix (HLH) and ETS DNA binding domains of ETV6 are present in the predicted BTL-ETV6 fusion protein, and the chimeric gene is transcribed from the BTL promoter.

Acute Disease↗

PubMed1999

Genomic organization of human JAK2 and mutation analysis of its JH2-domain in leukemia.

The Janus kinase family of proteins, with four mammalian members (JAK1, JAK2, JAK3 and TYK2), plays an essential role in the signal transduction pathway from non-catalytic cytokine receptors to the nucleus. We recently reported the involvement of ETV6-JAK2 fusion genes in the development of leukemia of both lymphoid and myeloid origin. Dominant missense mutations of hopscotch, a Drosophila JAK homologue, causing leukemia-like defects were described. One of these mutations affected a conserved residue of the kinase- like JH2 domain and the introduction of this mutation in murine Jak2 resulted in the constitutional activation of its kinase activity. In order to further analyze its role in leukemogenesis, we cloned human JAK2 and determined its genomic organization. Twenty-four exons spanning a region of approximately 150 kb were identified. A mutation analysis of the exons 13 to 19, encoding the kinase-like JH2 domain failed to detect activating mutations in leukemia samples, suggesting that this is a rare event in human leukemia.

Blotting, Northern↗

PubMed1997

Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia.

Translocations in hematologic disease of myeloid or lymphoid origin with breakpoints at chromosome band 12p13 frequently result in rearrangements of the Ets variant gene 6 (ETV6). As a consequence either the ETS DNA-binding domain or the Helix-Loop-Helix (HLH) oligomerization domain of ETV6 is fused to different partner genes. We show here that a t(9;12)(p24;p13) in a case of early pre-B acute lymphoid leukemia and a t(9;15;12)(p24;q15;p13) in atypical chronic myelogenous leukemia in transformation involve the ETV6 gene at 12p13 and the JAK2 gene at 9p24. In each case different fusion mRNAs were found, with only one resulting in an open reading frame for a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the protein tyrosine kinase (PTK) domain of JAK2. The cloning of the complete human JAK2 coding and genomic sequences and of the genomic junction fragments of the translocations allowed a characterization of the different splice events leading to the various mRNAs. JAK2 plays a central role in non-protein tyrosine kinase receptor signaling pathways, which could explain its involvement in malignancies of different hematologic lineages. Besides hop in Drosophila no member of the JAK family has yet been implicated in tumorigenesis.

Amino Acid Sequence↗

PubMed1992

Emotional arousal and overeating in restrained eaters.

We tested the effects of 3 mood inductions (neutral, positive, and negative) on food intake in 91 women of varying degrees of dietary restraint. Mood induction was accomplished by exposure to 1 of 3 film segments: a travelogue (neutral affect), a comedy film (positive affect), and a horror film (negative affect). In subjects exposed to the neutral film, food intake decreased with increasing levels of dietary restraint. Among subjects who viewed either the comedy film or the horror film, however, food intake increased with increasing restraint. Although the horror film appeared to be more disinhibiting than the comedy film, this effect may have resulted from a difference in the intensity of the emotions induced rather than from their valence. These results suggest that emotional arousal, regardless of valence, may trigger overeating among restrained eaters.

Adult↗

PubMed1990

Film-induced negative affect triggers overeating in restrained eaters.

We tested the effects of film-induced negative affect (i.e., exposure to a frightening film) in 60 women classified as either restrained or unrestrained eaters on the basis of their responses to the Revised Restraint Scale (Herman & Polivy, 1980). Exposure to the frightening film, in contrast to a neutral film, was associated with increases in anxiety, sadness, and anger. High restraint subjects exposed to the frightening film ate more than did equally restrained subjects exposed to a neutral film or low restraint subjects exposed to either film. Thus, negative affect triggered overeating among restrained eaters. Although unrestrained eaters exposed to the frightening film ate less than those who viewed the neutral film, this difference was not statistically significant. These results suggest that negative affect may prompt overeating in persons who attempt to restrict their caloric intake.

Adult↗

PubMed1990

Problem-solving deficits in suicidal patients: trait vulnerability or state phenomenon?

A diathesis-stress model has been proposed (Schotte & Clum, 1982, 1987), in which deficits in interpersonal problem-solving skills are said to predispose individuals under chronic stress to depression, hopelessness, and suicide ideation. The present study examined the stability of interpersonal problem-solving skills in a short-term, longitudinal study of hospitalized suicide ideators (N = 36). The Ss displayed marked changes in depressive symptoms, state anxiety, hopelessness, and suicide intent over time, and these improvements were associated with improvements in interpersonal problem-solving skills. It is concluded that interpersonal problem-solving deficits may be a concomitant, rather than a cause, of depression, hopelessness, and suicide intent.

Adult↗