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Biomedical subjects

C Bailly

Publications and source records attributed to C Bailly.

At least 271 records · Page 15Linked to original sources

Synthesis, biological activity and DNA interaction of anilinoacridine and bithiazole peptide derivatives related to the anti-tumor drugs m-AMSA and bleomycin.

The synthesis of two depsipeptides including a peptide metal-chelating moiety (Gly-His-Lys) and a moiety with DNA affinity, namely either glycyl-anilino-9-aminoacridine 1 or 2'-(2-aminoethyl)-4-methoxycarbonyl-2",4'-bithiazole 2, has been carried out. The goal was to introduce separately on the same molecule the two factors contributing to the biological activity of many anti-tumor drugs. The interaction of both drugs with DNA has been studied and the acridine ring of 1 was found to intercalate in the double helix. The production of free radicals has been evidenced by spin-trapping for 1 although both compounds were revealed to be good copper-chelating agents. In vitro cytostatic activity and inhibition of [3H]-thymidine incorporation were obtained for 1 while 2 exhibited no activity in both tests. In view of these results, it can be pointed out that the anti-tumor properties of such drugs rely (1) on their ability to reach and to bind DNA and (2) on redox mechanisms involving interactions between the drugs, metals and molecular oxygen. The latter phenomenon leads to the formation of active radical species, able to degrade the DNA.

Aminoacridines↗

[Antibiotic resistance plasmids from Serratia marcescens and their elimination by DNA-gyrase inhibitors].

We studied the effects of ciprofloxacin on 73 strains of Serratia marcescens. In the first place, we have tested their plasmidic content: 76% of Serratia marcescens strains contained plasmids by electrophoresis, and 29% of these plasmids were self-transmissible by conjugation. Secondly, we studied the plasmid stability with regard to ciprofloxacin. We obtained a spontaneous cure with 19% of plasmids, and ciprofloxacin, at very low concentrations (0.4 mg/l), increased the rate of cure and more efficiently than novobiocin, a compound used as a known curing agent.

Bacterial Typing Techniques↗

The role of the gulose-mannose part of bleomycin in activation of iron-molecular oxygen complexes.

A comparison of the complexing properties of metal ions and O2 activation by bleomycin-A2 (BLM-A2) and deglyco-BLM-A2 is presented. Deglyco-BLM-A2 is obtained from the parent derivative by HF cleavage of the sugar moiety followed by h.p.l.c. purification. Complexing of Cu(II) and Fe(III) is studied by using c.d. and e.s.r. spectroscopy. Spin-trapping experiments in the presence of phenyl N-t-butylnitrone indicated lower production of free radicals by deglyco-BLM-A2. Finally, a proposal is made to explain this discrepancy, focusing on the probable role of the gulose-mannose moiety acting as a protecting pocket, comparable with the pocket and picket-fence porphyrins described for haemoproteins.

Bleomycin↗

DNA-binding and DNA-cleaving properties of a synthetic model AGAGLU related to the antitumour drugs AMSA and bleomycin.

We have previously described two synthetic models gathering a simplified model of the complexing part of Bleomycin (Blm) and the intercalating moiety of m-AMSA. These molecules, namely AGGA and AGAMGA, do not seem able to cleave DNA as Blm does. The present work is devoted to the study of a new derivative, AGAGLU, which includes in its structure a judiciously chosen connector between the two parts of the molecule. This compound, the chelating and DNA-binding properties of which are described here, has been shown to induce single-strand breakage of duplex DNA in a high level.

Aminoacridines↗

Immunocytochemical detection of neuroblastoma cells infiltrating clinical bone marrow samples.

To evaluate the feasibility and clinical usefulness of immunocytochemical detection of bone marrow metastases in neuroblastoma, we studied bone marrow samples from patients undergoing intensive therapy, followed in the majority of cases by autologous bone marrow rescue. Two monoclonal antibodies were used in an indirect immunoenzymatic assay to test 384 samples collected from multiple bone marrow sites during 79 staging procedures in 48 patients. Of 578 immunocytochemical tests, 59 (10%) yielded non-evaluable results. Analysis by individual bone marrow sites showed an agreement between cytological and immunocytochemical examinations in 276 of 309 (89%) evaluable tests with 5 A7 and in 179 of 210 (85%) with UJ 13 A. Infiltration by neuroblastoma cells was reported in 9% of samples by cytology, in 6% by immunochemistry with 5 A7 and in 16% with 13 A. Analysis of results by staging demonstrated agreement between cytological examination and immunocytochemical detection with both monoclonal antibodies in 60 of 75 (80%) evaluable stagings. Bone marrow metastasis was detected by cytology in 22% of stagings, by immunochemistry with 5 A7 in 23%, with UJ 13 A in 25%. Detailed analysis of discordant results revealed that they were related partly to bone marrow sampling variability associated with focal and minimal metastasis of neuroblastoma cells. These data suggest the clinical usefulness of immunocytochemical detection as a complementary test to cytological examination for accurate evaluation of bone marrow infiltration in patients with disseminated neuroblastoma.

Antibodies, Monoclonal↗

Differential effects of ADH on sodium, chloride, potassium, calcium and magnesium transport in cortical and medullary thick ascending limbs of mouse nephron.

The effect of antidiuretic hormone (arginine vasopressin, AVP) on transepithelial Na+, Cl-, K+, Ca2+ and Mg2+ net transports was investigated in medullary (mTAL) and cortical (cTAL) segments of the thick ascending limb (TAL) of mouse nephron, perfused in vitro. Transepithelial net fluxes (JNa+, JCl-, JK+, JCa2+, JMg2+) were determined by electron probe analysis of the collected tubular fluid. Transepithelial potential difference (PDte) and transepithelial resistance (Rte) were measured simultaneously. cTAL segments were bathed and perfused with isoosmolal, HCO3- containing Ringer solutions, mTAL segments were bathed and perfused with isoosmolal HCO3- free Ringer solutions. In cTAL segments, AVP (10(-10) mol.l-1) significantly increased JMg2+ and JCa2+ from 0.39 +/- 0.08 to 0.58 +/- 0.10 and from 0.86 +/- 0.13 to 1.19 +/- 0.15 pmol.min-1 mm-1 respectively. Neither JNa+ nor JCl-, (JNa+: 213 +/- 30 versus 221 +/- 28 pmol.min-1 mm-1, JCl-: 206 +/- 30 versus 220 +/- 23 pmol.min-1 mm-1) nor PDte (13.4 +/- 1.3 mV versus 14.1 +/- 1.9 mV) or Rte (24.6 +/- 6.5 omega cm2 versus 22.6 +/- 6.4 omega cm2) were significantly changed by AVP. No significant effect of AVP on net K+ transport was observed. In mTAL segments, Mg2+ and Ca2+ net transports were close to zero and AVP (10(-10) mol.l-1) elicited no effect. However NaCl net reabsorption was significantly stimulated by the hormone, JNa+ increased from 107 +/- 33 to 148 +/- 30 and JCl- from 121 +/- 33 to 165 +/- 32 pmol.min-1 mm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differentiation of normal and tumoral human keratinocytes cultured on dermis: reconstruction of either normal or tumoral architecture.

Normal human keratinocytes isolated from skin and squamous carcinoma cells established from a human tumor (TR146 cell line) both exhibit limited morphologic differentiation when they are grown on conventional plastic dishes. However, when they are seeded on human de-epidermized dermis and cultured at the air-liquid interface, they are able to reform an epithelium having the morphology of the tissue of origin (i.e. skin or squamous carcinoma). The distribution in such reconstructed tissues of differentiation markers such as bullous pemphigoid antigen, 67K keratin, involucrin, membrane-bound transglutaminase, and filaggrin was very similar to their distribution in normal skin and squamous carcinoma specimens, respectively. The degree of differentiation is for both cell types extremely sensitive to culture conditions such as retinoic acid concentration, emersion of the cultures, etc. These results show that subcultured normal or tumoral keratinocytes are able to recover their specific morphogenetic potential when cultured in an environment close to their in vivo situation.

Antigens, Surface↗

DNA-synthesis and tumor growth inhibitions by AGGA, a bleomycin-amsacrine hybrid derivative.

AGGA, [[(amino-2-ethyl)-2-aminomethyl]-2-pyridine-6-carboxylhistidyl-ami no-4- butyrylglycylamino]-4-phenyl-1-amino-9-acridine is a synthetic model gathering the simplified metal-chelating part of bleomycin and the intercalating moiety of amsacrine. This molecule was found to possess the metal-complexing and intercalative properties of both antitumor parent drugs. On the basis of results obtained on L1210 and HeLa S3 cells growth inhibition studies and labeled thymidine assay, AGGA clearly indicates a cytostatic activity. On the other hand, the oxygenated free radicals produced in the presence of iron and oxygen do not seem to be able to cleave DNA as BLM does. This lack of cytotoxicity is analyzed in terms of fundamental differences between BLM and AGGA-DNA complexes.

Aminoacridines↗

[Serological study of the virus responsible for hemorrhagic fever in an urban population of Cameroon].

A sero-epidemiological study of Hemorrhagic Fever Viruses in a urban population of Cameroon. The authors report the results of a sero-epidemiological survey undertaken in a urban population of Cameroon and concerning Congo, Rift (RVF), Lassa, Ebola, Marburg and Yellow Fever Viruses. On 375 human sera tested, 1.06% show antibodies against RVF virus and 1.87% are positive for anti-Ebola antibodies thus yielding evidence that these two viruses are present in this area of Cameroon. 33.75% have antibodies against Yellow Fever Virus as determined with an Hemagglutination-inhibition test. This quite high percentage, in spite of the weak specificity of the method for this virus, could raise the problem of the opportunity of a vaccination campaign. No antibody to Marburg, Lassa or Congo viruses is detected.

Adolescent↗

[Value of immunological analysis for the detection of residual neuroblasts in the bone marrow].

Immunological analysis is complementary of morphological analyses in the detection of neuroblastoma BM metastases. It attests the neuroblastic nature of rare pseudolymphocytic isolated cells. The combination of immunocytochemical technique (alkaline phosphate) and double-immunofluorescence technique allows the detection of as few as 10(-5) residual neuroblastoma cells. At the time of bone marrow harvest, it permits a precise evaluation of malignant cells in the graft.

Bone Marrow↗

Complexation of copper(II) by a peptide hybrid of bleomycin and amsacrine. Circular dichroism and electron spin resonance studies.

A model incorporating the metal chelating moiety of bleomycin and an anilinoacridine ring able to intercalate in DNA has been synthesized. The copper(II) complex of that molecule has been studied using circular dichroism and electron spin resonance by comparison with bleomycin. The introduction of the anilinoacridine ring involves a modification in the geometry of the complex. A distortion of the square-pyramidal form (type II complex) gives rise to a type I complex in which the metallic atom is drawn out of the plane of the four square-planar ligands and displaced slightly towards the fifth ligand.

Bleomycin↗

Design of two metal-chelating, DNA-binding models: molecular combinations of bleomycin and amsacrine anti-tumour drugs.

In the course of studies on bleomycin, we recently showed that the bithiazole ring is a poor intercalator into DNA. Therefore we have designed new models, replacing this heterocyclic moiety by an anilinoacridine ring in order to increase the affinity for DNA. This work presents results obtained for two model compounds showing (i) that the anilinoacridine nucleus leads to a good stabilization of the DNA helix, and (ii) that the presence of a bulky group near the complexing part of bleomycin is essential to the activation of molecular oxygen.

Amsacrine↗

[Detection of residual cells contaminating the bone marrow in neuroblastoma. Apropos of 80 bone marrow evaluations].

Eighty bone marrow studies (each including 4 aspirates and 4 trephine biopsies) were performed in 37 children with stage IV neuroblastoma to assess the most accurate means for detection of invasion by neuroblastoma cells. Among 38 abnormal results, only trephine biopsy(ies) were found positive in 24 cases (63%), only aspirate(s) in 5 cases (13%), and both in 9 cases (24%). In 37% of abnormal results, only 1 of the 8 tests performed was found positive. No benefit was obtained from either associated touch imprints of iliac biopsies (67 investigations), or exploration of extra-iliac sites (66 sternums, 53 tibias). Two monoclonal antibodies, claimed to be specific for detection of neuroblastoma cells in bone marrow, were used in 56 investigations; they could detect minimal residual disease in some cases, but they were unreliable when no staining was obtained if initial phenotype of neuroblastoma had not been assessed, or when few isolated cells were observed. Prospective studies using immunocytology and immunohistology are thus warranted.

Antibodies, Monoclonal↗

Expression of high molecular weight (67K) keratin in human keratinocytes cultured on dead de-epidermized dermis.

The influence of living dermal tissue upon epidermal differentiation during embryonic development as well as in vitro culture has been documented. Living dermal tissue contains both cellular and matricial elements. In the present study, third-passage subcultured adult human keratinocytes were either seeded on plastic dishes or recombined with dead de-epidermized dermis and further cultured for 3 weeks. After this time, keratins were extracted and analysed by one- and two-dimensional gel electrophoresis. The 67K keratin subunit, which is thought to be involved in the process of in vivo type skin differentiation, was absent in ordinary cultures; however, it was expressed in air-exposed cultures on dead de-epidermized dermis. Quantitatively, however, it did not reach the in vivo level. This suggests that in principle, the induction of the expression of this protein does not require the presence of living dermal cells.

Adult↗