PubMed Health⌕ Search

Biomedical subjects

F Fleury

Publications and source records attributed to F Fleury.

At least 37 records · Page 2Linked to original sources
PubMed1997

Camptothecin-binding site in human serum albumin and protein transformations induced by drug binding.

Circular dichroism (CD) and Raman spectroscopy were employed in order to locate a camptothecin (CPT)-binding site within human serum albumin (HSA) and to identify protein structural transformations induced by CPT binding. A competitive binding of CPT and 3'-azido-3'-deoxythymidine (a ligand occupying IIIA structural sub-domain of the protein) to HSA does not show any competition and demonstrates that the ligands are located in the different binding sites, whereas a HSA-bound CPT may be replaced by warfarin, occupying IIA structural sub-domain of the protein. Raman and CD spectra of HSA and HSA/CPT complexes show that the CPT-binding does not induce changes of the global protein secondary structure. On the other hand, Raman spectra reveal pronounced CPT-induced local structural modifications of the HSA molecule, involving changes in configuration of the two disulfide bonds and transfer of a single Trp-residue to hydrophilic environment. These data suggest that CPT is bound in the region of interdomain connections within the IIA structural domain of HSA and it induces relative movement of the protein structural domains.

Binding Sites↗
PubMed1997

Interactions of lactone, carboxylate and self-aggregated forms of camptothecin with human and bovine serum albumins.

Pronounced differences in the interactions of monomeric (lactone and carboxylate) and the J-type self-aggregated form of camptothecin (CPT), an inhibitor of DNA topoisomerase (topo) I, with human (HSA) and bovine (BSA) serum albumins were observed by using circular dichroism (CD) spectroscopy. HSA binding changes the geometry of the covalent structure of CPT due to hydrophobic contacts of the chromophore within the protein interior. The carbonyl group of the ring D of CPT (Fig. 1A) interacts with the positively charged amino acid residues of HSA. Interaction with HSA induces disaggregation of the J-type self-aggregates of CPT. On the other hand, neither heat-denatured HSA nor native BSA participated in binding of the lactone or carboxylate or self-aggregate forms of CPT. Analysis of HSA and BSA homology within the IIA and IIIA principle ligand-binding structural domains suggests that the binding site for the CPT chromophore is located in subdomain IIA. Hydrophobic contacts with Leu-203, Phe-211, and Ala-215 and electrostatic interactions with Lys-199 and/or Arg-222 of HSA may play a key role in formation of the drug-HSA complex.

Amino Acid Sequence↗
PubMed1997

Localization and molecular interactions of mitoxantrone within living K562 cells as probed by confocal spectral imaging analysis.

Studying mechanisms of drug antitumor action is complicated by the lack of noninvasive methods enabling direct monitoring of the state and interactions of the drugs within intact viable cells. Here we present a confocal spectral imaging (CSI) technique as a method of overcoming this problem. We applied this method to the examination of localization and interactions of mitoxantrone (1, 4-dihydroxy-5, 8-bis-[([2-(2-hydroxyethyl)-amino]ethyl)amino]-9,10-anthracenedione dihydrochloride), a potent antitumor drug, in living K562 cells. A two-dimensional set of fluorescence spectra of mitoxantrone (MITOX) recorded with micron resolution within a drug-treated cell was analyzed to reveal formation of drug-target complexes and to create the maps of their intracellular distribution. The analysis was based on detailed in vitro modeling of drug-target (DNA, RNA, DNA topoisomerase II) interactions and environmental effects affecting drug fluorescence. MITOX exposed to aqueous intracellular environment, MITOX bound to hydrophobic cellular structures, complexes of MITOX with nucleic acids, as well as the naphtoquinoxaline metabolite of MITOX were simultaneously detected and mapped in K562 cells. These states and complexes are known to be immediately related to the antitumor action of the drug. The results obtained present a basis for the subsequent quantitative analysis of concentration and time-dependent accumulation of free and bound MITOX within different compartments of living cancer cells.

Antineoplastic Agents↗
PubMed1997

Quantitative confocal spectral imaging analysis of mitoxantrone within living K562 cells: intracellular accumulation and distribution of monomers, aggregates, naphtoquinoxaline metabolite, and drug-target complexes.

Confocal spectral imaging (CSI) technique was used for quantitative analysis of the uptake, subcellular localization, and characteristics of localized binding and retention of anticancer agent mitoxantrone (MITOX) within human K562 erythroleukemia cells. The CSI technique enables identification of the state and interactions of the drug within the living cells. Utilizing this unique property of the method, intracellular distributions were examined for monomeric MITOX in polar environment, MITOX bound with hydrophobic cellular structures, naphthoquinoxaline metabolite, and nucleic acid-related complexes of MITOX. The features revealed were compared for the cells treated with 2 microM or 10 microM of MITOX for 1 h and correlated to the known data on antitumor action of the drug. MITOX was found to exhibit high tendency to self-aggregation within intracellular media. The aggregates are concluded to be a determinant of long-term intracellular retention of the drug and a source of persistent intracellular binding of MITOX. Considerable penetration of MITOX in the hydrophobic cytoskeleton structures as well as growing accumulation of MITOX bound to nucleic acids within the nucleus were found to occur in the cells treated with a high concentration of the drug. These effects may be among the factors stimulating and/or accompanying high-dose mitoxantrone-induced programmed cell death or apoptosis.

Antineoplastic Agents↗
PubMed1997

[Migrant child].

Explore the source record for details and available documents.

Child↗
PubMed1996

DNA topoisomerase I changes the mode of interaction between camptothecin drugs and DNA as probed by UV-resonance Raman spectroscopy.

Pronounced differences of interactions of camptothecin (CPT) and its derivative 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT11), inhibitors of DNA topoisomerase I, with oligonucleotides were found using UV resonance Raman spectroscopy. 30-mer oligonucleotides were derived from the sequences of the topoisomerase I-induced and CPT-enhanced cleavage sites in SV40 DNA. CPT induces well-defined alterations of the oligo structure, whereas CPT11 interacts with oligonucleotides more weakly and in another manner than CPT. Formation of cleavable ternary complexes between CPT11, topoisomerase I and oligonucleotides causes CPT11 to interact with oligonucleotides in the same fashion as was found for its parent compound CPT, and enhances this interaction as compared to CPT-oligonucleotide complexes. The data present evidence of molecular interactions of CPT11 with both other partners (topoisomerase I and oligonucleotide) of the ternary cleavable complex at the oligonucleotide-enzyme interface.

Antineoplastic Agents, Phytogenic↗
PubMed1996

[Radiotherapy and curietherapy of squamous cell carcinoma of the posterior pharyngeal wall (excluding the nasopharynx)].

From 1986 to 1992, 55 cases of PPWC were treated with a conservative intent at the Regional Cancer Center (Rennes, France) and Saint-Yves Center (Vannes, France): 16 oropharyngeal posterior wall carcinoma (OP) and 39 hypopharyngeal posterior wall (HP); the mean age of the population was 60.3 years (31-81 years). A previous and simultaneous head and neck cancer was noted in 15 and 13% of cases respectively. Half of the cases (55%) were T1 T2 tumors and 82% were N0 N1. Except for three patients treated by curietherapy (5%), all patients were treated by radiotherapy (RT) alone (75%) or associated with curietherapy (7%) or partial pharyngectomy (13%). 15% received neoadjuvant chemotherapy, mainly for T3 tumors. With a followup of 4-88 months (mean: 23 months) 38% of patients are still alive; 8% of loco-regionally controlled patients died of second cancer or intercurrent disease. The tumor control was 67%. The nodes control was 90%. During the course of the disease, 19% of patients had metastases. The complete response at the end of treatment was 78%. Among these patients, 54% remained definitively free of disease. There is no difference between OP and HP. The analysis of survival curves showed the following points: significant difference between T1 T2, and T2 T3 (P < 0.05), N0 N1 and N2 N3 (P < 0.03), well differentiated histology or not (P < 0.02), RT alone or associated with curietherapy or surgery (P < 0.03) even for limited tumors T1 T2 N0 N1 (P < 0.03). There was no significant difference between group treated or not by chemotherapy even for T3 tumors. These findings do not differ if we consider either OP or HP. We conclude that OP and HP have the same prognostic factors and must be considered as the same clinical entity. For limited tumors T1 T2 N0 N1, patients managed by radiotherapy associated with complementary local treatment (conservative surgery or curietherapy) do better than patients treated by RT alone (plateau 80% at 18 months+vs plateau 25% at 12 months +). For these limited tumors, our recommendation is to treat patients by external RT (50 Gy) and curietherapy boost (20 Gy) rather than by conservative surgery and external RT (70 Gy). These two treatments have the same efficacity but the first one is expected to diminish late complications of RT. Neo adjuvant chemotherapy does not seen to improve survival even for advanced tumors. Generally speaking these results remain poor for locally advanced desease and for undifferentiated tumors. These patients need a new therapeutic approach (concomittant radio-chemotherapy, hyper or hypofonctionnated RT).

Adult↗
PubMed1996

[Cancers of the base of the tongue and hypopharynx: results of a multicenter randomized trial of chemotherapy prior to locoregional treatment].

The authors report the results of a multicentric randomised trial assessing the effects on survival of neoadjuvant chemotherapy with cisplatin (100 mg/m2, D1) and fluorouracil (1 g/m2, D2-4) delivered before regional treatment in patients with squamous cell carcinoma of hypopharynx and base of tongue. 133 patients were enrolled in the study, and 121 were included in the analysis, 64 in group A (regional treatment alone) and 27 in group B (chemotherapy followed by regional treatment). Despite a high objective response rate to chemotherapy (primary tumour: 85%, 24% complete; nodes: 63%), overall survival was not significantly higher in group B than in group A.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Health promotion for immigrants in Switzerland.

Migration, especially when it is forced, involves hardships and health needs that cannot always be met by the existing local services. An association in Lausanne creatively combines preventive, educational and therapeutic activities for asylum seekers, refugees and immigrants.

Emigration and Immigration↗
PubMed1995

Genetic variation in locomotor activity rhythm among populations of Leptopilina heterotoma (Hymenoptera: Eucoilidae), a larval parasitoid of Drosophila species.

The locomotor activity rhythm of Leptopilina heterotoma, a parasitoid insect of Drosophila larvae, was investigated under laboratory conditions. Under LD 12:12, the locomotor activity of females shows a clear rhythm which persists under continuous darkness (circadian rhythm). However, comparative study of five populations indicates that both the rate of activity and the profile of the rhythm vary according to the origin of females. The Mediterranean populations (Tunisia and Antibes) show two peaks of activity, at the beginning and at the end of the photophase, whereas more northern populations (Lyon and the Netherlands) are mostly active during the afternoon. Females originating from the area of Lyon have a very low level of activity. Reciprocal crosses (F1 hybrids and backcrosses) between the French and the Tunisian strains demonstrated the genetic basis of these variations and the biparental inheritance of the trait. This genetic variability is interpreted as a consequence of selective pressures and suggests a local adaptation of natural populations in host foraging behavior. The selective factors which could act on the daily organization of parasitoid behaviors are discussed.

Activity Cycles↗
PubMed1993

[Evaluation of AIDS-related knowledge and behavior among seasonal workers in Switzerland].

Although an increasing number of AIDS prevention programmes are addressing migrants and ethnic minorities, few are either solidly research-based or adequately evaluated. Reported on here is a baseline evaluation of a marginal foreign population, Spanish and Portuguese seasonal workers in Switzerland. AIDS-related knowledge, attitudes and behaviours were assessed with both qualitative and quantitative methods during the winter of 1989-1990. The seasonal workers studied had been reached by prevention programmes both in the host country and in the country of origin, and knowledge was better than expected. Zones of ambiguity, such as confusion between AIDS and treatable STDs, persist however. Legal restrictions which prohibit family reunification affect sexual behavior: respondents report both more abstinence and more transitory sexual relations than the comparison Swiss population. Only about one in five report always using condoms during transitory relations. Qualitative material is used to suggest a relation between attitudes and protective behaviors. HIV/AIDS prevention programmes for Spanish and Portuguese populations in Switzerland are being established on the basis of the research findings.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Changes in plasma progesterone in female Vipera aspis L. (Reptilia, Viperidae) during the sexual cycle in pregnant and nonpregnant females.

The plasma progesterone concentration in female Vipera aspis changes during pregnancy and exhibits an increase before ovulation, a summer peak, a decrease up to parturition, and a new increase at the beginning of hibernation. For females in their first or second year after gestation, the evolution of plasma progesterone shows a spring peak and a summer peak. Whatever the stage of the sexual cycle, females present two annual periods of steroidogenic activity producing plasma progesterone: one in spring and one in summer. All data suggest an annual endogenous endocrinological cycle of reproduction, modulated by external factors (temperature, food availability). The origin of plasma progesterone and its control in the sexual cycle are discussed.

Animals↗
PubMed1989

Evaluation of the clinical performance of three triphasic oral contraceptives: a multicenter, randomized comparative trial.

Three hundred thirteen women participated in an open, multicenter comparison of the incidence of intermenstrual bleeding (breakthrough bleeding and or spotting) associated with the use of three triphasic oral contraceptives. Triphasil (n = 107), containing levonorgestrel and ethinyl estradiol, and Ortho-Novum 7/7/7 (n = 97) and Tri-Norinyl (n = 109), both of which contain norethindrone and ethinyl estradiol, were administered over four cycles for a total of 1141 cycles. The total incidence of intermenstrual bleeding was significantly lower with Triphasil (17.2%) than with Ortho-Novum 7/7/7 (39.5%) or Tri-Norinyl (49.0%). The pattern remained the same when findings were analyzed cycle by cycle and for breakthrough bleeding and spotting separately. The incidence of other side effects was comparable for all regimens. Results of this study demonstrate superior cycle control with Triphasil compared with Ortho-Novum 7/7/7 and Tri-Norinyl during the first four cycles of use.

Adolescent↗
PubMed1987

[Relations between hibernation and the resumption of endocrine, testicular and thyroid activities, in Vipera aspis L. (Reptilia, Viperidae)].

The relationships between the end of hibernation and testicular and thyroid endocrine recrudescence were tested in Vipera aspis by subjecting hibernating vipers to experimental climatic conditions. Vipers kept under artificially warmed conditions (for 3.5 hr during the day to a thermal gradient from 11 to 27 degrees) 1 month before emergence showed an increase in plasma testosterone before vipers exposed to natural conditions (outdoor enclosures) did. The use of different photoperiodic conditions, long, LD 12:12, and short, LD 8:16, shows that photoperiod length has no effect on this increase. For vipers kept under prolonged hibernation (under a uniform temperature of 5 degrees or exposed to natural conditions at the northern limit of the species' distribution), testicular endocrine recrudescence was observed as soon as the first emergence only for the vipers placed at the northern range limit. Whatever the conditions, experimental or natural, the emergence of vipers always corresponds to a weight loss correlated with the increase of plasma thyroxine level. The relationship between the end of hibernation and testicular and thyroid endocrine recrudescence is discussed.

Animals↗
PubMed1987

Annual cycles in plasma testosterone and thyroxine in the male aspic viper Vipera aspis L., (Reptilia, Viperidae), in relation to the sexual cycle and hibernation.

Blood samples were taken monthly from males of Vipera aspis kept in outdoor terraria. Plasma testosterone was estimated by radioimmunoassay and plasma thyroxine by the technique of isotopic competition, between October 1979 and September 1985. Plasma testosterone showed an annual bimodal profile. The highest peak was observed from February 15 to the end of March. 2 to 5 weeks after the first emergence from hibernation. Values then decreased greatly, to reach a minimum level when the vernal spermiogenesis was at its maximum. The secondary peak of plasma testosterone was lower and less well marked. It occurred at the end of summer, during the strongest spermiogenesis, and preceded the autumnal facultative mating period. Plasma thyroxine was at a maximum concentration from February to March after which levels decreased markedly. The seasonal profile of plasma thyroxine was clearly marked during the period of hibernation. From September to October, 2 months before the beginning of hibernation, thyroxine levels began to decrease, and they reached a minimum in November-December. Endocrine reactivation of the thyroid appeared at the end of hibernation. However, in contrast to the plasma testosterone, endocrine activity of the thyroid began 2 to 3 weeks before the end of hibernation. Mechanisms of reactivation for testicular and thyroidal endocrine structures are discussed.

Animals↗
PubMed1985

Therapeutic results obtained in vaginal mycoses after single-dose treatment with 500 mg clotrimazole vaginal tablets.

A multicenter, double-blind study of 103 patients with clinically and mycologically documented vulvovaginal candidiasis compared single-dose treatment with a 500 mg clotrimazole vaginal tablet to 3-day treatment with two 100 mg clotrimazole vaginal tablets administered daily. Patients were examined 5 to 10 days (visit 2) and at least 27 days (visit 3) post treatment. At visit 2, mycologic and clinical examinations were negative in 43 of 48 efficacy-evaluable patients receiving clotrimazole, 500 mg (90%), versus 42 of 47 efficacy-evaluable patients receiving clotrimazole, 200 mg (89%). Similarly, at visit 3, 75% of patients receiving clotrimazole, 500 mg, had treatment success versus 72% receiving clotrimazole, 200 mg. There were no significant intergroup treatment differences, indicating that single-dose treatment with clotrimazole, 500 mg, is equipotent to the multidose regimen.

Adolescent↗