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D Coen

Publications and source records attributed to D Coen.

26 records · Page 2Linked to original sources

Plasminogen activator activity of metastatic variants from a murine fibrosarcoma; effect of thrombin in vitro.

In order to investigate the possible correlation between plasminogen activator (PA) activity and metastatic potential of tumour cells, we studied cultured cells from the murine fibrosarcoma mFS6 and from its two sublines M4 and M9 which differ markedly in their capacity to cause spontaneous metastases in the lung. PA activity was detected in all the sublines by an amidolytic method and was almost completely inhibited by treatment with antiurokinase antiserum. No significant differences were shown between mFS6, M4 and M9. Moreover, molecular analysis of PA by SDS-PAGE electrophoresis and fibrin overlay revealed in all the cell types a single species having a mol. wt. of approximately 48,000 daltons. Thrombin treatment dramatically inhibited the amidolytic activity of all cells, suggesting a role for this enzyme in the modulation of fibrin formation and dissolution within the primary neoplasm.

Animals↗

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Mitochondrial genetics. XI. Mutations at the mitochondrial locus omega affecting the recombination of mitochondrial genes in Saccharomyces cerevisiae.

1. A series of CS revertants has been selected from various strains (both omega+ and omega-) carrying a CR mitochondrial mutation at the RIB1 locus. The properties of mitochondrial recombination exhibited by these CS revertants in various crosses, have been examined systematically. The omega allele of the CS revertants has been defined in crosses with omega+ and omega- tester strains using two criteria: the polarity of recombination and a new criterium called relative output coefficient. We found that mutations of omega appear frequently associated with the mutations at the RIB1 locus selected from omega- strains but not with those selected from omega+ strains. A new allelic form of omega (omega n) which had not been found amongst wild type yeast strains is characterised. Similarly omega n mutation was found frequently associated with CR mutants at the RIB1 locus selected from omega- CS strains but not with those selected from omega+ CS strains. The omega n mutants, and the omega+ and omega- strains, explain the groups of polarity previously observed by Coen et al. (1970). 2. Main features of mitochondrial crosses with omega n strains (omega+ x omega n, omega- x omega n and omega n x omega n) are analysed. Recombination is possible between the different mitochondrial genetic markers. No high polarity of recombination is observed and the frequency of recombinants are similar to those found in homosexual crosses (omega+ x omega+ and omega- x omega-). A striking property, observed for the first time, exists in crosses between zota+ omega n CS strains and some zota- CREO mutants: the zota- CREO are unable to integrate by recombination their CR allele into the zota+ mit-DNA of omega n CS strains while being capable of integrating it into omega+ CS or omega- CS genomes. 3. It is proposed that the omega locus is the site of initiation of non reciprocal recombination events, the omega+/omega- pairing specifically initiates the non-reciprocal act while omega+/omega n or omega-/omega n pairings do not. 4. The molecular nature of the omega n mutation and its bearing on the structure of the omega locus are discussed. It is suggested that omega n mutations correspond to macrolesions (probably deletions) of a segment of the mit-DNA covering the omega and RIB1 loci. If omega n is a partial deletions of the omega- sequence the omega+ could be an additionnal deletion of the omega n sequence. 5. The occurrence of spontaneous CR and ER mitochondrial mutations has been analysed by the Luria and Delbrück fluctuation test in omega- and omega n isonuclear strains. Results of these tests indicate that an intracellular selection of resistant copies preexisting the action of the anttibiotic occurs.

Alleles↗

Mitochondrial genetics. VI. The petite mutation in Saccharomyces cerevisiae: interrelations between the loss of the p+ factor and the loss of the drug resistance mitochondrial genetic markers.

The survival of the rho(+) factor and of Drug(R) mitochondrial genetic markers after exposure to ethidium bromide has been studied. A technique allowing the determination of Drug(R) genetic markers among a great number of both grande and petite colonies has been developed. The results have been analyzed by the target theory. The survival of the rho(+) factor is always less than the survival of any Drug(R) genetic marker. The survivals of C(R) and E(R) are similar to each other, while that of O(R) is greater than that of the other two Drug(R) markers. All possible combinations of Drug(R) markers have been found among the rho(-) petite cells induced, while the only type found among the grande colonies is the preexisting one. The loss of the C(R) and E(R) genetic markers was found to be the most frequently concomitant, while the correlation between the loss of the O(R) marker and the other two Drug(R) markers is less strong. Similar results have been obtained after U.V. irradiation. Interpretations concerning the structure of the yeast mitochondrial genome are given and hypotheses on the mechanism of petite mutation discussed.

Drug Resistance, Microbial↗

Mitochondrial genetics. VII. Allelism and mapping studies of ribosomal mutants resistant to chloramphenicol, erythromycin and spiramycin in S. cerevisiae.

We have isolated 15 spontaneous mutants resistant to one or several antibiotics like chloramphenicol, erythromycin and spiramycin. We have shown by several criteria that all of them result from mutations localized in the mitochondrial DNA. The mutations have been mapped by allelism tests and by two- and three-factor crosses involving various configurations of resistant and sensitive alleles associated in cis or in trans with the mitochondrial locus omega which governs the polarity of genetic recombination. A general mapping procedure based on results of heterosexual (omega(+)x omega(-)) crosses and applicable to mutations localized in the polar segment is described and shown to be more resolving than that based on results of homosexual crosses. Mutations fall into three loci which are all linked and map in the following order: omega-R(I)-R(II)-R(III). The first locus is very tightly linked with omega while the second is less linked to the first. Mutations of similar resistance phenotype can belong to different loci and different phenotypes to the same locus. Mutations confer antibiotic resistance on isolated mitochondrial ribosomes and delineate a ribosomal segment of the mitochondrial DNA. Homo- and hetero-sexual crosses between mutants of the ribosomal segment and those belonging to the genetically unlinked ATPase locus, O(I), have been performed in various allele configurations. The polarity of recombination between R(I), R(II), R(III) and O(I) decreases as a function of the distance of the R locus from the omega locus rather than as a function of the distance of the R locus from the O(I) locus.

Adenosine Triphosphatases↗