[Toxicity of high-dose methotrexate. Pharmacokinetic data].
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Adult↗
Biomedical subjects
Y Pommier
Publications and source records attributed to Y Pommier.
Inhibitors of poly-(adenosine diphosphoribose) synthesis slow the resealing rate of x-ray-induced DNA strand breaks.
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Animals↗
High doses of cytosine arabinoside (HD-Ara-C) as reinforcement during remission of acute myeloid leukemia.
High doses of Cytosine-arabinoside (Ara-C) (1 to 3gm/m2 every 12 hours during 48 hours) were administered monthly to 5 acute myeloid leukemia patients during complete remissions subsequent to relapses and reinduction treatment. Plasma Ara-C was measured using a radioimmunoassay and exhibited kinetics compatible with a bi- or tri- compartimental model. Tolerance was good, with mainly gastrointestinal toxicity and somnolence. The duration of remissions was relatively long, taking into account that these were second or third remissions.
Adult↗
Interaction between mianserin and clonidine at alpha 2-adrenoceptors.
The purpose of the present study was to characterize the effects of mianserin at alpha 2-adrenoceptors. Firstly, the action of mianserin on postganglionic sympathetic fibres has been studied using the tachycardia induced by stimulation of the cardiac nerve in dogs. Mianserin increased this tachycardia, but could not prevent the inhibitory effect of clonidine in this model. However, an antagonistic effect of mianserin against clonidine was observed when animals were pretreated with desipramine. Secondly, mianserin antagonized the inhibitory effect of clonidine on the electrically stimulated guinea-pig ileum. In high concentrations, mianserin reduced both electrically and acetylcholine induced contractions. Thirdly, mianserin antagonised the sleep induced by clonidine in chickens. These results are consistent with alpha 2-adrenoceptor blocking properties of mianserin in peripheral noradrenergic fibres in dogs, in cholinergic fibres in guinea-pig ileum and in the central nervous system in chickens.
Animals↗
Effects of some alpha-adrenoceptor agonists and antagonists on the guinea-pig ileum.
The purpose of the present study was to further characterize the alpha-adrenoceptors located on parasympathetic fibres. Segments of guinea-pig ileum were stimulated by transmural electrical pulses, and the ensuing contractions, which are due to the release of acetylcholine from postganglionic parasympathetic fibres, were monitored. Clonidine and tramazoline, which are thought to act preferentially on presynaptic alpha-adrenoceptors, reduced the contractions, whereas phenylephrine and methoxamine, postsynaptic alpha-adrenoceptor agonists, were ineffective. Contractions induced by acetylcholine were not changed by clonidine but were abolished by atropine. Yohimbine, piperoxan, phentolamine and the thymoxamine reversed or prevented the inhibitory effect of clonidine. Prazosin and AR-C239 did not antagonize this effect. The inhibitory effect of tramazoline was antagonized by piperoxan but not AR-C239 or by prazosin. Naloxone did not alter the action of clonidine, and piperoxan did not change the inhibitory effect of morphine. In conclusion, these experiments suggest the presence on cholinergic postganglionic fibres of both opiate receptors and alpha-adrenoceptors.. The latter appear to resemble more closely alpha 2-adrenoceptors than alpha 1-adrenoceptors.
Acetylcholine↗
Evidence of a reduced DNA topoisomerase II mRNA expression after ionizing radiation.
DNA topoisomerase II (top2) is a nuclear enzyme which resolves the topological constraints during DNA metabolism and is the target of some of the most active drugs used in cancer chemotherapy. Top2 is regulated both transcriptionally and post-transcriptionally and its expression is coupled to cell cycle position. To explore the regulation of top2 after DNA damage, we studied the behavior of cell lines of the National Cancer Institute Anticancer Drug Screen, previously characterized for p53 status, in response to ionizing radiation. The kinetics of top2 mRNA expression were measured using quantitative hybridization. A profound and transient decrease of top2 mRNA after irradiation was detected within four hours in 30% of the 25 cell lines tested. This transient top2 decrease in mRNA expression occurred independently of the p53 status of the cell lines and was not associated with increased apoptotic DNA fragmentation. This observation indicates that a transient decrease in top2 mRNA expression may occur after DNA damage and suggests the need for preferential schedule when planning the use of top2 inhibitors with ionizing radiation during combined radio-chemotherapy treatments.
Apoptosis↗
[Very long survivals of chronic granulocytic leukemia (author's transl)].
Following busulfan induced bone marrow insufficiency, a patient witha chronic granulocytic leukemia (CGL) has had a survival lasting 18.5 years. During remission, chromosome studies on bone marrow have not shown Philadelphia chromosome (Ph 1). There was no correlation between this observation and initial pronostic factors from literature. Analysis of 14 cases (13 from literature) of prolonged survival showed that Ph 1 was absent in 4 cases when only 15% of CGL are initially Ph 1 negative. Therapeuticcaryoconversions were probable. Recently attempts have been made to eradicate the abnormal Ph 1 positive clone. Some hopeful results are reported.
Adult↗