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Biomedical subjects

J C David

Publications and source records attributed to J C David.

At least 55 records · Page 3Linked to original sources
PubMed1985

Molecular duality of DNA ligase in axolotl corresponds to distinctive transcriptional information.

Based upon the use of specific antibodies and sucrose gradient sedimentation analysis, the present work describes the use of the post-transcriptional equipment of the urodele egg to compare the information contained in two RNA samples extracted from respectively liver and activated axolotl eggs. It is shown that besides the normal DNA ligase activity present in the host Pleurodeles eggs, RNA can translate for the specific carried information revealing a difference between the two samples. Moreover, unlike in nuclear transplantation, the homologous DNA ligases are not mutually exclusive. These observations give a new convincing support of the genetic basis of the molecular duality of DNA ligases.

Ambystoma↗
PubMed1985

DNA ligases in human leukemia.

Following partial purification on sucrose gradient and/or phosphocellulose chromatography, DNA ligase was tested in peripheral white blood and bone marrow cells of nearly 100 patients with various kinds of leukemias, mainly acute leukemias. Terminal deoxynucleotidyl transferase (TdT) was tested in parallel. DNA ligase of acute myeloblastic leukemia (AML) was extracted with the same sedimentation coefficient (5.5S) on sucrose gradient, and eluted with the same KCl molarity (0.3 M) than the one extracted from normal lymphocytes. Acute lymphoblastic leukemias (ALL) were characterized by no detectable DNA ligase activity--in most T or non T-non B-ALL, or a low activity in pre-B and B (Burkitt type) ALL, with levels similar to the one observed in chronic lymphocytic leukemia (CLL). An inverse relationship was observed between DNA-ligase and TdT in ALL, ligase being undetectable in cells positive for TdT and being present in some T or non T-non B, and in all pre-B and B-ALL negative for TdT. AML and chronic myelocytic leukemia (CML) were characterized by a markedly higher DNA-ligase activity. This activity was higher in the most differentiated subtypes--M2, M3 and M4 subtypes of FAB classification--and in CML. Moreover a high degree of correlation was observed in AML between the DNA ligase activity and the S phase fraction measured by 3 H-thymidine autoradiography or flow cytophotometry on the total cell sampling. Besides their clinical interest, these results are discussed in relation with the role of DNA-ligase in DNA replication and repair.

Adolescent↗
PubMed1985

Effects of antileukemic agents on the activity of terminal deoxynucleotidyl transferase from human normal thymic and leukemic cells "in vitro".

Several widely used and experimental antileukemic drugs have been tested on the activity of Terminal deoxynucleotidyl Transferase (TdT) purified from normal human thymocytes and T-derived acute lymphoblastic leukemia peripheral blood lymphoblasts. The majority of these inhibitors were equally potent inhibitors of the enzyme from thymocytes or leukemic lymphocytes. Adriamycine and etoposide were more potent inhibitors of the enzyme purified from thymocytes. Vincristine was a more potent inhibitor of TdT extracted from leukemic lymphocytes than from thymocytes. These results are discussed in terms of possible functions for TdT in the two types of cells and on the value of TdT as an indicator for clinical treatment.

Adolescent↗
PubMed1985

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Allergy and Immunology↗
PubMed1985

Inhibition of DNA ligase from human thymocytes and normal or leukemic lymphocytes by antileukemic drugs.

Human DNA ligase was purified from both normal and leukemic peripheral lymphocytes and normal thymocytes. The activity of the purified enzymes was assayed in the presence of several widely used antileukemic drugs. Melphalan and prednisone at 5 mM had no effect. Carmustine, chlorambucil, and cyclophosphamide were more effective at inhibiting the enzyme from leukemic cells, whereas Adriamycin and vinblastine and their derivatives were stronger inhibitors of the enzyme from normal cells. Vincristine and etoposide inhibited DNA ligase from thymocytes and normal lymphocytes with a low Ki but were totally ineffective on the enzyme from leukemic cells. The three classes of intercalating anthracyclines, Vicia alkaloids, and podophyllotoxin derivatives, were the only drugs found to markedly inhibit DNA ligases from normal cells. Less substituted molecules of the Vicia alkaloids and podophyllotoxin classes were the more active inhibitors, whereas in the intercalating anthracycline group, it was the more substituted compounds. The clinical consequences of these observations are discussed with respect to the role of DNA ligase in DNA replication and repair.

Antineoplastic Agents↗
PubMed1984

Quinolone antibiotics inhibit eucaryotic DNA polymerase alpha and beta, terminal deoxynucleotidyl transferase but not DNA ligase.

DNA polymerases alpha and beta, Terminal deoxynucleotidyl Transferase and DNA ligases from chicken thymus were purified to homogeneity. Quinolone antibiotics (nalidixic acid, oxolinic acid and pefloxacin ) known to inhibit DNA replication were tested for their effects on these enzymes. DNA ligase activity was not affected by the three drugs. DNA polymerases alpha and beta were inhibited by competitive mechanisms. Surprisingly, Terminal deoxynucleotidyl Transferase was strongly inhibited by the three compounds and more efficiently by nalidixic acid. The significance of these results is discussed in terms of the possible involvement of the enzymes in the respective DNA replication and repair processes.

Animals↗
PubMed1984

Prenatal ontogenesis of p-, m-octopamine and phenylethanolamine in relation to catecholamines and their metabolizing enzymes in the developing rat brain and heart.

Non-catecholamines such as phenylethanolamine and p-octopamine are present in many invertebrate nervous systems, sometimes in large amounts. These amines are normally present in the rat brain at much lower levels, p- and m-octopamine are present at trace levels in the mammalian brain. The prenatal development of these amines was studied in comparison with those of noradrenaline and dopamine. The activities of tyrosine hydroxylase, dopa decarboxylase, dopamine beta-hydroxylase and monoamine oxidase were determined in parallel. Phenylethanolamine and p-octopamine are more abundant in the brain between 13 and 17 fetal days than dopamine and noradrenaline but decrease after 17 days whereas the levels of m-octopamine and the two catecholamines increase afterwards. Dopa decarboxylase, dopamine beta-hydroxylase and tyrosine hydroxylase are detected early in fetal life (13, 15 and 14.5 days respectively) but monoamine oxidase activity was not found before 18 days.

2-Hydroxyphenethylamine↗
PubMed1984

In vitro occurrence of m-octopamine in the cultured cephalic ganglion of Locusta migratoria L. after L-dopa administration.

Cephalic ganglia of the locust Locusta migratoria L. were cultured in the presence of L-DOPA and inhibitors of dopa decarboxylase or dopamine beta hydroxylase. The addition of L-DOPA to the culture medium resulted in a marked increase of m-octopamine, following higher levels of dopamine. L-DOPA produced an increase of m-tyramine. RO 44602 considerably reduced the levels of p and m-octopamines, m-tyramine, dopamine and noradrenaline while fusaric acid reduced only those of p and m-octopamines, m-tyramine and noradrenaline. Though not normally found in the locust nervous system, m-octopamine appears to be closely related to catecholamines and to be produced via their biosynthesizing enzymes through a hypothetical dehydroxylation step.

Animals↗
PubMed1984

Developmental regulation of phenylethanolamine N-methyl transferase in avian sympathetic nerves.

The presence of the catecholamine synthetic enzyme, phenylethanolamine N-methyl transferase (PNMT), has been detected in the expansor secundariorum, a smooth muscle of the avian wing. The concentration of the enzyme was estimated over a 10-week time course from 17 days incubation to 9 weeks posthatch and found to increase rapidly up until hatch in parallel with dopamine beta-hydroxylase activity, but then to fall precipitously to very low levels. The time course of the initial increase in activity corresponds to the presence of ingrowing sympathetic nerve fibres, and denervation of the expansor results in loss of greater than 80% of the PNMT activity. It is concluded that during the period of innervation the growing nerves contain the enzyme PNMT and therefore have the capacity to synthesize adrenaline, but that shortly after innervation is complete the capacity to synthesize adrenaline is lost. Several alternate mechanisms are proposed to explain the observations.

Adrenergic Fibers↗
PubMed1984

Relationship between phenolamines and catecholamines during rat brain embryonic development in vivo and in vitro.

p-Octopamine and phenylethanolamine are present in the embryonic rat brain earlier than catecholamines. These phenolamines are localized mainly in the hypothalamus, where the level of p-octopamine is very high. The parallel developmental study of the activities of dopamine beta-hydroxylase, 3,4-dihydroxyphenylalanine decarboxylase, tyrosine hydroxylase, and monoamine oxidase shows that phenolamines are present in significant amounts in the hypothalamus until tyrosine hydroxylase and monoamine oxidase become catalytically active. The culture of embryonic hypothalamus at different ages shows that no tyrosine hydroxylase and monoamine oxidase activities can be detected if the tissue is cultured before 15 days. This clearly indicates that all the enzymes related to catecholamine biosynthesis are not triggered at the same time during the development of the rat brain. These results are discussed on the basis of the physiological importance of phenolamines in mammals and of the use of the developing rat brain as a model for the study of the onset of the catecholaminergic system and the decline of the octopamine.

Animals↗
PubMed1983

Brain octopamine and strain differences in avoidance behavior.

According to recent research, a significant relationship seems to exist between brain contents of p-octopamine and two-way avoidance responding in rats. Levels of this amine in hypothalamus and brainstem are higher in rats from the Roman High Avoidance (RHA) strain than in rats from the Roman Low Avoidance (RLA) strain. Intracerebroventricular administration of p-octopamine facilitates avoidance responding. The present paper reports the behavioral and neurochemical effects of p-octopamine administration on rats from the Roman strains. This treatment has no significant effect on cerebral levels of catecholamines, but it temporarily suppresses the strain differences in p-octopamine levels. In parallel, it also suppresses the strain differences in two-way avoidance conditioning, its facilitatory effect being much greater in RLA than in RHA rats. Avoidance behavior appears to be a useful model for the study of octopamine functions in the mammalian brain.

Animals↗
PubMed1983

Isolation of the messenger RNA for 8S DNA ligase in early developing axolotl egg and its cell free translation.

A new DNA ligase activity is expressed when the Axolotl eggs enter cleavage. The messenger RNA can be labelled by [3H] uridine thereby indicating its de novo synthesis. This new genetic expression is occurring just before cleavage and is the earliest found during Amphibian development. The newly synthesized [3H] mRNA can be translated in vitro in the rabbit reticulocyte lysate system. The resulting product is a 160 K protein specifically immunoprecipitated with the antiserum directed against 8S DNA ligase. This in vitro translated polypeptide exhibits 8S DNA ligase activity specific of activated or fertilized eggs but does not display 6S DNA ligase activity of non activated eggs.

Ambystoma↗
PubMed1983

DNA ligase in Axolotl egg: a model for study of gene activity control.

Replacement of the light form of DNA ligase (6 S) by the heavy form (8 S) in activated egg of Axolotl has been studied as a model for change in genetic activity exerted by the female pronucleus. Nuclear transplantation shows that a blastula nucleus is able to govern the replacement of the light ligase by the heavy one. The result is not the same if the grafted nucleus is taken from an androgenetic embryo, devoid of the heavy enzyme. Therefore the change in the properties of the female pronucleus appears stable and autoreproducible. Gamma irradiations delivered at different times after activation establish that the replacement of the ligase forms depends on an intact nucleus up to 3 hr 30 min after activation, and thereafter is achieved independently of any nuclear damage. Inhibitors of DNA replication impede the change of enzymatic form in reversible process, suggesting new chromatin synthesis as prerequisite for expression of the new genetic activity. The quantitative level of DNA ligase activity does not show any dose effect when one or many nuclei are present in the same cytoplasm. However, a change in nucleotide concentration results in a change in DNA ligase activity, indicating cytoplasmic control of enzymatic regulation.

Ambystoma↗
PubMed1983

Control of DNA ligase molecular forms in nucleocytoplasmic combinations of axolotl and Pleurodeles.

A light form of DNA ligase (EC 6.5.1.2), the only form present in oocytes of the axolotl (Ambystoma mexicanum), has been shown to be replaced by a heavy form of the enzyme when the egg enters cleavage. This early biochemical event has been assumed to rely on direct nuclear input. Sucrose gradient analysis permits discrimination between enzymes from axolotl and the sharp-ribbed salamander (Pleurodeles waltlii) for both heavy and light enzymatic forms of DNA ligase. Genetic activity of blastula nuclei transplanted in activated cytoplasm has been tested by determination of the enzymatic forms and specific types of DNA ligases when the implanted egg enters cleavage. A blastula nucleus of Pleurodeles in axolotl cytoplasm determines a heavy ligase of the Pleurodeles type. Conversely, a haploid androgenetic nucleus of Pleurodeles in axolotl cytoplasm controls a light ligase of the Pleurodeles type. Reciprocal experiments give homologous results. To our knowledge, this is the earliest nucleus-dependent synthesis revealed in development for any system. The heavy ligase of one species may coexist with the light form of the other species but not with the light form of its own specific type. Inhibition of the production of the heavy form for one genome results in the expression of the light form. We conclude that genetic control of DNA ligase in very early development involves structural genes for heavy and light forms of enzyme, with an exclusion process operating an alternative expression of corresponding genes. This exclusion relationship between nonallelic genes is species specific.

Ambystoma↗
PubMed1982

Behavioural and neurochemical effects of intracerebroventricular administrations of p-octopamine in rats.

Intracerebroventricular administration of p-octopamine (250 micrograms) had opposite effects on locomotor activity of rats depending on whether or not the animals were submitted to electric shocks in the experimental situation. When rats were not shocked, their locomotor activity was significantly decreased by the injection. On the other hand, when rats were trained in a shuttle-box, administration of p-octopamine significantly increased avoidance responding and intertrial crossings. The neurochemical effects of the injections were relatively specific: they significantly increased p-octopamine levels in hypothalamus and brainstem but little effect was observed on noradrenaline and dopamine brain contents. These data suggest that octopamine may play the role of a neuromodulator in the central nervous system of mammals.

Animals↗