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J Van den Akker

Publications and source records attributed to J Van den Akker.

At least 19 recordsLinked to original sources
PubMed2006

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique.

Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.

Adolescent↗
PubMed2006

NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique.

The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.

Adolescent↗
PubMed2004

Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia.

Imatinib mesylate (Gleevec), an inhibitor of the BCR-ABL tyrosine kinase, was introduced recently into the therapy of chronic myeloid leukemia (CML). Several cases of emergence of clonal chromosomal abnormalities after therapy with imatinib have been reported, but their incidence, etiology and prognosis remain to be clarified. We report here a large series of 34 CML patients treated with imatinib who developed Philadelphia (Ph)-negative clones. Among 1001 patients with Ph-positive CML treated with imatinib, 34 (3.4%) developed clonal chromosomal abnormalities in Ph-negative cells. Three patients were treated with imatinib up-front. The most common cytogenetic abnormalities were trisomy 8 and monosomy 7 in twelve and seven patients, respectively. In 15 patients, fluorescent in situ hybridization with specific probes was performed in materials archived before the initiation of imatinib. The Ph-negative clone was related to previous therapy in three patients, and represented a minor pre-existing clone that expanded after the eradication of Ph-positive cells with imatinib in two others. However, in 11 patients, the new clonal chromosomal abnormalities were not detected and imatinib may have had a direct effect. No myelodysplasia was found in our cohort. With a median follow-up of 24 months, one patient showed CML acceleration and two relapsed.

Adult↗
PubMed1994

Autologous bone marrow transplantation in ALL: relapse linked to infusion of tumor cells with the back-up marrow.

A 41-year-old female patient with a pre-B ALL expressing 2 BCR/ABL transcripts e1/a2 and b2/a2 underwent autologous bone marrow transplantation (aBMT) with marrow grown in long-term culture (LTC) for consolidation of remission (CR). After failing to engraft on day 54 she received her back-up marrow. She engrafted by day 23 and developed a full-blown leukemic relapse 2 weeks later. She died from tumor progression 3 months after infusion of the backup marrow. Analysis of the BCR/ABL transcripts weakly positive at time of collection of the backup marrow, negative in the LTC marrow and in the patient after infusion of the LTC marrow, again positive from day 29 after infusion of the backup marrow until death, strongly suggests that infusion of residual tumor cells with the backup marrow contributed to the relapse.

Adult↗
PubMed1993

A novel genetic thrombocytopenia (Paris-Trousseau) associated with platelet inclusions, dysmegakaryopoiesis and chromosome deletion AT 11q23.

We report a novel case of hereditary thrombocytopenia. A chronic thrombocytopenia was noted in a woman with mild hemorrhagic complications as well as in her very young son. A platelet fraction contained giant granules stained in red on blood smears. The number of bone marrow megakaryocytes was increased with many micromegakaryocytes. Since the platelet life span was normal, these results indicated an ineffective platelet production. A constitutional cytogenetic abnormality was detected in the two patients: a deletion of the long arm of chromosome 11. The association of these abnormalities constitute a new disorder: this never described cytological entity is a valuable model for exploring the role of some genes involved in the regulation of thrombopoiesis.

Adult↗
PubMed1992

Calcium release from separate receptor-specific intracellular stores induced by histamine and ATP in a hamster cell line.

1. The specificity of intracellular Ca2+ stores to Ca(2+)-mobilizing agonists was studied in DDT1 MF-2 vas deferens cells of the Syrian hamster. 2. Application of histamine (100 microM) or ATP (100 microM) to the DDT1 MF-2 cells caused an initial increase of intracellular Ca2+ followed by a lower phase as measured by using Indo-1 as fluorescent probe at 22 degrees C. The basal Ca2+ level (146 nM) was enhanced to 309 nM by histamine and to 379 nM by ATP. 3. A transient rise in intracellular Ca2+ lasting for about 2 min was measured in the presence of histamine or ATP in the absence of extracellular Ca2+. The basal Ca2+ level (78 nM) was increased to 128 nM by histamine and to 145 nM by ATP. 4. A transient hyperpolarization was elicited in single cells as measured with microelectrodes by both agonists under Ca(2+)-free conditions with a similar time course as the change in internal Ca2+. The hyperpolarization observed in the presence of histamine amounted to 23 mV and 31 mV with ATP. The histamine-induced responses were abolished by the H1 histaminoceptor antagonist mepyramine (10 microM) and the responses evoked by ATP were blocked by the P2 purinoceptor antagonist suramin (300 microM). 5. A second internal Ca2+ response could only be evoked under Ca(2+)-free conditions by applying a higher agonist concentration or after replenishing the intracellular stores with Ca2+ from the extracellular space. 6. A second addition of an optimal concentration (100 microM) of the agonist to the cells under Ca(2+)-free conditions did not evoke mobilization of internal Ca2+ or hyperpolarization, but resulted in a rise of the cellular inositol (1,4,5)-trisphosphate content (Ins(1,4,5)P3) as determined by a radioligand binding assay. 7. The cells responded to both agonists (100 microM) with a transient Ca2+ response if successively applied at a maximal effective concentration (100 microM) under Ca(2+)-free conditions. 8. Simultaneous stimulation of H1 histaminoceptors and P2 purinoceptors resulted in the absence of external Ca2+ in an additional increase in internal Ca2+ represented by the amplitude and area of the response and in an increased response area of the hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1992

Juvenile chronic myelocytic leukemia with unusual cytogenetic clonal evolution.

Cytogenetic studies are reported in a case of juvenile chronic myelocytic leukemia with dysmyelopoiesis and skin involvement. The clonal evolution of a 6q-anomaly is described. Hematological and cytogenetic findings suggest a role of hematopoietic stem cell in this patient for whom the outcome was fatal.

Child, Preschool↗
PubMed1989

Effect of cromakalim on smooth muscle cells of guinea-pig taenia caeci.

Cromakalim caused hyperpolarization and reduction of the electrotonic potential in a concentration-dependent manner in smooth muscle cells of guinea-pig taenia caeci. There was a relatively constant change in the electrotonic potential under calcium-free, low-sodium and low-chloride conditions in the presence of cromakalim as compared to control conditions with Krebs solutiuon. The effect of cromakalin (10(-5) M) was inhibited by glibenclamide (5 X 10(-5) M). These results indicate that cromakalim specifically promotes potassium efflux in smooth muscle cells of the guinea-pig taenia caeci via glibenclamide-sensitive potassium channels, to cause hyperpolarization, suppression of spike activity and relaxation.

Animals↗
PubMed1989

Suramin and the inhibitory junction potential in taenia caeci of the guinea-pig.

The effect of surinam on the inhibitory junction potential evoked in smooth muscle cells of guinea-pig taenia caeci by stimulation of intramural nerves at 22 degrees C was investigated. The amplitude of the inhibitory junction potential was reduced concentration dependently by suramin. The suppression of this response by suramin became less pronounced when the number of stimuli increased (pulse rate: 20/s). These results indicate that suramin reduces the inhibitory junction response by interacting with P2-purinoceptors.

Adenosine Triphosphate↗
PubMed1989

Characterization of the UV-induced electrophysiological response in smooth muscle.

The effect of ultraviolet (UV) light on taenia caeci smooth muscle of guinea-pig was studied. This stimulus induced a decrease in membrane conductance, hyperpolarization of the smooth muscle cells, a decrease in spike activity and a diminished level of cGMP and enhancement of lipid peroxidation. The hyperpolarization evoked by UV light was attenuated in the presence of sodium nitrite, reaching a maximum at 0.5 mM sodium nitrite. The level of cGMP was enhanced in the presence of nitrite and lipid peroxidation was not changed. Under these conditions lipid peroxidation was not changed during UV irradiation either. The UV-induced hyperpolarization was abolished in the absence of extracellular calcium, inhibited in the presence of 8-Br-cGMP and enhanced by an increase in the extracellular calcium concentration. These results are consistent with the supposition that UV-A irradiation blocks calcium influx via a cGMP-dependent mechanism.

Animals↗
PubMed1989

The inhibitory action of suramin on the P2-purinoceptor response in smooth muscle cells of guinea-pig taenia caeci.

The effect of suramin on the smooth muscle cell response of guinea-pig taenia caeci to P2-purinoceptor and alpha 1-adrenoceptor stimulation was measured. The ATP-induced relaxation in potassium (20 mM) pre-contracted taenia caeci was inhibited by suramin (3 x 10(-4) M). The P2-purinoceptor-induced hyperpolarization elicited by ATP both in the presence and absence of calcium was also reduced by suramin. The alpha 1-adrenoceptor-mediated relaxation evoked by phenylephrine was only affected by suramin at low concentrations of the agonist. The results indicate that suramin inhibits the ATP response by interacting with P2y-purinoceptors.

Adenosine Triphosphate↗
PubMed1988

The multiple action of bradykinin on smooth muscle of guinea-pig taenia caeci.

The action of bradykinin on the smooth muscle of guinea-pig taenia caeci was studied by measuring changes in membrane potential, the contractile state of the muscle cells and intracellular calcium concentrations at 22 degrees C in the presence of tetrodotoxin, yohimbine, prazosin, propranolol and atropine. The bradykinin response was characterised by an initial hyperpolarization and suppression of spike activity followed by a sustained depolarization and an increased spike activity accompanied by inhibition of the phasic contractions, an increase in muscle tone and the development of phasic contractions, respectively. The actions of bradykinin were not affected after B1-bradykinin receptors were blocked with des-Arg9-[Leu8]bradykinin. The events induced by bradykinin were accompanied by an increase in the intracellular calcium concentration, as monitored by quin-2 fluorescence. The hyperpolarization and depolarization persisted in the presence of diltiazem (10(-5) M) and in calcium-free conditions. The hyperpolarization could be evoked only once in the absence of calcium and was inhibited in the presence of apamin and after stimulation of alpha 1-adrenoceptors or P2-purinoceptors. Membrane conductance was decreased during the sustained depolarization. The membrane depolarization was abolished after the sodium concentration gradient was reduced. These results show a multiple action of bradykinin mediated via B2-receptors: (1) on calcium mobilization associated with activation of potassium channels; (2) on calcium release from intracellular stores and (3) on receptor-activated sodium channels.

Animals↗
PubMed1987

The action of some new aminopyridines on mammalian non-myelinated nerve fibres.

The effects of a recently synthesized series of aminopyridines 2-methyl-4-AP, 2-chloro-4-AP and 2-(N,N-methyl-benzyl)amino-4-AP (2A-7) on voltage-operated sodium and potassium channels and on the sodium pump activity of non-myelinated fibres of the guinea-pig vagus nerve were studied with the sucrose-gap method. The compound action potential evoked by electrical stimulation and the propagation velocity along the nerve were not affected by 2-methyl-4-AP or 2-chloro-4-AP up to a concentration of 10(-3) M. The post-tetanic potential (PTH) evoked by repetitive stimulation of the nerve and reflecting sodium pumping was also not affected by these agents. The amplitude and duration of the compound action potential were enhanced to some extent by 2-methyl-4-AP at the highest concentration used (3 X 10(-3) M); this action was also observed and was more pronounced with 4-aminopyridine (4-AP). The other aminopyridine 2A-7 (3 X 10(-5) - 3 X 10(-4) M) caused suppression of the compound action potential, a diminished propagation velocity and a reduction of the PTH, an action also observed with lidocaine. These results show that 2-methyl-4-AP and 3-chloro-4-AP did not affect the voltage-operated sodium or potassium channels in non-myelinated fibres of the vagus nerve. Only 2-methyl-4-AP had a small 4-AP-like action at high concentrations. The aminopyridine 2A-7 possesses a local anaesthetic action as reflected by the inhibition of voltage-operated sodium channels.

Action Potentials↗
PubMed1987

The action of mebeverine and metabolites on mammalian non-myelinated nerve fibres.

The effect of mebeverine, mebeverine-alcohol and veratric acid on voltage-operated ion channels and on sodium pump activity were studied. The amplitude and duration of the compound action potential evoked in the vagus nerve were decreased by mebeverine but not by the metabolites. The amplitude of the post-tetanic hyperpolarization was decreased by mebeverine while the time constant of decay, representing sodium-potassium pump activity, was not affected by the compounds tested. These results show that mebeverine exerts a local anaesthetic action by blocking voltage-operated sodium channels.

Action Potentials↗
PubMed1987

Modification of alpha 1-receptor-operated channels by mebeverine in smooth muscle cells of guinea-pig taenia caeci.

Changes in the potential and contractility of smooth muscle cells of guinea-pig taenia caeci were measured (22 degrees C) in order to investigate the effect of mebeverine, a derivative of beta-phenylethylamine, on alpha 1-receptor-operated ion channels in particular. Mebeverine (6 X 10(-6) M) showed atropine-like properties by shifting to the right the concentration-response curve obtained with carbachol. Hyperpolarization and cessation of spike activity of the muscle cells, accompanied by an increased amplitude of the electrotonic potential were observed in the presence of mebeverine (6 X 10(-5] after block of the alpha 2-, beta- and muscarinic receptors. This effect of mebeverine was not observed in low-sodium solution (23.8 mM), suggesting that mebeverine decreased sodium permeability. The alpha 1-receptor-induced hyperpolarization caused by adrenaline (3 X 10(-6) M) in the presence of mebeverine declined after reaching an initial maximum. The hyperpolarization induced by a second addition of adrenaline to the preparation was decreased and sustained in the presence of mebeverine, while the decrease of the electrotonic potential evoked during the alpha 1 response was less pronounced. The transient hyperpolarization representing the alpha 1 response in the absence of extracellular calcium developed more slowly in the presence of mebeverine, the area of the response being constant. When the experiment was continued in calcium-free solution after a short exposure to calcium-containing Krebs solution still in the presence of mebeverine, the alpha 1-receptor-induced hyperpolarization was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The action of procainamide and quinidine on the alpha 1-receptor-operated channels in smooth muscle cells of guinea-pig taenia caeci.

The effect of procainamide (2.0-5.0 mM) and quinidine (0.2-1.0 mM) on the alpha 1 response evoked by adrenaline (3 X 10(-6) M) in smooth muscle cells of guinea-pig taenia caeci (22 degrees C) was studied in the presence of yohimbine (3 X 10(-6) M), propranolol (3 X 10(-6) M) or atropine (10(-6) M). The electrotonic potential elicited by the application of a constant current to the preparation was slightly increased (about 10%) by procainamide (5.0 mM) but not by quinidine (1.0 mM). The double-sucrose gap method was used for measurements. The alpha 1 response evoked by adrenaline in the absence of extracellular calcium (15 min) was represented by a transient hyperpolarization of the muscle cells, while the hyperpolarization elicited in the presence of calcium was sustained. The hyperpolarization is caused by enhancement of the potassium efflux assumed to be linked with mobilization of calcium form a cellular structure. Superfusion of the preparation with calcium-containing solution to replenish the calcium store in the presence of procainamide (10 min) before the alpha 1 response evoked in the absence of calcium and procainamide did not affect the transient hyperpolarization. Quinidine, however, suppressed the alpha 1 response when the same procedure was followed. Both the transient and the sustained hyperpolarization evoked in smooth muscle cells in the presence of procainamide (15 min) or quinidine in calcium-containing or in calcium-free solution, respectively, were inhibited. The alpha 1 response was reflected by a depolarization of the muscle cells after the potassium channels had been blocked with apamin (3 X 10(-7) M, 20 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗