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Biomedical subjects

J Deregnaucourt

Publications and source records attributed to J Deregnaucourt.

9 recordsLinked to original sources

Synthesis and antisecretory and antiulcer activities of derivatives and analogues of 2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide.

New thioamide derivatives of 2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide (29) and related compounds (in which the tetrahydrothiophene ring was replaced by tetrahydrothiopyran, tetrahydrofuran, 1,3-dithiane, or 1,3-oxathiane and where the pyridine ring was replaced by other nitrogen heterocycles) were synthesized and tested for their antisecretory and antiulcer activities. These thioamides were prepared according to one of the following methods: reaction of an isothiocyanate with the carbanion of the corresponding cyclic precursor (for secondary thioamides); reaction of ammonia or an amine with the dithio ester prepared from the same precursor (for primary, secondary, and tertiary thioamides). These thioamides were evaluated by the Shay method to measure their antisecretory activity and by the stress-induced-ulcer method to test their antiulcer activity. Structure-activity relationships are discussed. N-Methyl-2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide (R.P. 40749, 30) exhibited activities that were at least 10 times higher than those reported for cimetidine.

Animals↗

Distribution of 250 cases of acute myeloid leukaemia (AML) according to the FAB classification and response to therapy.

250 consecutive cases of AML in adults were diagnosed over a 6 year period in the same institution. Pretreatment blood and bone marrow smears and also cytochemical markers were taken into account in the study. All cases were reviewed by three different observers and classified according to the FAB criteria. The final diagnosis resulted from agreement of at least two observers. Some discrepancies occurred in the classification and are discussed. The prognostic implication of AML subclassification was assessed as the percentage of complete remission in 100 cases.

Adolescent↗

Proliferation in liquid culture of myeloid progenitor cells from the blood of normals and patients with aplastic anaemia.

We studied myeloid progenitor cells (CFUc) from peripheral blood mononuclear leukocytes (MNL) of normals and patients with severe aplastic anaemia (AA). Baseline CFUc averaged 4.4 +/- 1.5 (range 0--17)/10(6) MNL in fifteen normals and 0 +/- 1/10(6) MNL in six patients with severe AA (P less than 0.05). To assess CFUc proliferative capacity, 10(7) MNL were put into liquid culture in Marbrook chambers with colony-stimulating activity and sub-cultured in agar at intervals up to 10 days. CFUc from normal MNL increased from 44 +/- 15/chamber at Day 0 to 156 +/- 33/chamber at peak value (P less than 0.02). In contrast, CFUc from AA MNL remained undetectable throughout the period of liquid culture (AA peak v. normal peak; P less than 0.001). These results indicate a marked decrease in circulating CFUc in patients with severe AA, and a profound abnormality in CFUc proliferation in vitro. This abnormality could be due to defective replication of CFUc, a lack of feed-in from more primitive precursors, or both.

Adult↗

An in vitro model of hematopoietic injury in chronic hypoplastic anemia.

Mice treated with high-dose busulfan develop a 'latent' form of bone marrow failure characterized by near-normal peripheral blood counts and marrow cellularity, but marked reductions in marrow pluripotent stem cells (CFUs) and myeloid progenitor cells (CFUc). Spleen cell suspensions from control and 'latent' mice were placed in liquid culture in the presence of colony-stimulating activity. Cells were harvested at intervals up to 14 days and sub-cultured in agar to assay for CFUc. Baseline splenic CFUc did not differ significantly between control and 'latent' mice. Splenic CFUc from control mice increased 50-fold and reached a peak at day 10 in liquid culture. In contrast, splenic CFUc from 'latent' mice increased only 7-fold and reached a peak at day 3. Our results indicate that although splenic CFUc are present in normal numbers in 'latent' mice, their proliferative capacity is markedly reduced, either as the result of defective CFUc self-renewal or defective feed-in from CFUs or both.

Anemia↗

Acute non myeloid leukaemia in adults. Prognostic factors in 92 patients.

An analysis of prognostic factors was performed on a series of 92 adult patients with acute non-myeloid leukaemia (ANML). Four factors were shown to be correlated with a poor short-term prognosis: (1) Neuropathy involving a single cranial nerve (numbness of the chin) as a presenting feature. (2) A low percentage blast cell infiltration of bone marrow (less than 55%). (3) Cytological L2 type or L3 type of cells according to FAB classification proposals. (4) Increased age. Two factors were shown to be correlated with a poor long-term prognosis: 1) A high level of circulating blast cells; 2) A high tumour burden, as in childhood ANML. These two long-term prognostic factors were interrelated. In addition, our results suggested that myelofibrosis could be a poor long-term prognosis factor as well.

Acute Disease↗

[Evidence for CFU-C self-replication (author's transl)].

To explore the proliferative potential of committed myeloid progenitor cells (CFU-C), we placed suspensions of mouse spleen cells in short-term liquid culture with colony stimulating activity and subcultured the cells in agar at intervals to assay for CFU-C. Prior to liquid culture, aliquots of spleen cells were exposed briefly to hypotonic conditions to lyse CFU-S but not CFU-C. A 50-fold increase in CFU-C was observed in control cultures. The pattern of CFU-C proliferation was not altered significantly by hypotonic lysis despite the fact that this treatment effectively removed CFU-S. These results support the hypothesis that CFU-C are capable of self-replication and permit a model of hematopoiesis in which expansion of the granulopoietic pool is controlled, in part, at the level of the CFU-C.

Animals↗

Protection by trimipramine against gastric mucosal barrier dysfunction induced by ethanol + HC1 in rats.

The effects of trimipramine (5 mg . kg-1 . h-1 intravenously) on the changes in gastric mucosal function evoked by 20% ethanol + HCl has been stuided in rats. The magnitude of the changes in potential difference, ionic fluxes (H+, Na+, and K+), and mucosal lesion score induced by ethanol + HCl were significantly less in animals treated with trimipramine than in control animals. It is concluded that trimipramine decreases the gastric mucosal damage produced the ethanol + HCl in rats. This activity may be responsible, at least in part, for the beneficial effect of trimipramine treatment in peptic ulcer disease.

Animals↗

Increased resistance of the gastric mucosal barrier to barrier breakers in the rat.

The effects of two exposures of the gastric mucosa to either 10 mM taurocholic acid (TcA) or 20% ethanol, both in 150 mM HCl, on transmucosal potential difference (PD) and net fluxes of H+, Na+, and K+ ions have been tested in the rat. The interval between exposures was 30 min. The results demonstrated that the first exposure of the gastric mucosa, either to TcA or to ethanol, reduced the net fluxes of H+, Na+, K+ and the change in transmucosal PD induced by the second exposure, indicating an increased resistance of the mucosa to the barrier breaking effects of TcA or ethanol.

Administration, Topical↗