Search PubMed⌕ Search

Biomedical subjects

M Raymond

Publications and source records attributed to M Raymond.

At least 73 records · Page 4Linked to original sources
PubMed1994

Resistance monitoring in Culex pipiens (Diptera: Culicidae) from central-eastern France.

Insensitive acetylcholinesterase (AceR) and five over-produced esterases (A1, A2 and B2, and A4 and B4) involved in detoxification are responsible for resistance to organophosphorous insecticides (OPs) in Culex pipiens L. from the Rhône-Alpes region, where C. pipiens control is mainly accomplished with the OPs temephos and chlorpyrifos using 0.15 mg/liter doses. The strong linkage disequilibria observed between esterases A1 and Est-20(0.64), esterases A4 and B4, and esterases A2 and B2 indicate that these genes were introduced in the Rhône-Alpes region. AceR and esterase A1, which appeared in the south of France 3 yr before the start of mosquito control in Rhône-Alpes, had the highest frequencies. All resistant genotypes were shown to be killed by 0.15 mg/liter temephos in natural breeding sites, but not by 0.15 mg/liter chlorpyrifos. These results are discussed in relation with mosquito control strategies.

Acetylcholinesterase↗
PubMed1994

Insecticide resistance genes in Culex pipiens (Diptera: Culicidae) from Italy: esterase B locus at the DNA level.

Restriction fragment length polymorphism (RFLP) analysis at the esterase B locus was performed in samples from four populations of Italian Culex pipiens pipiens L. to identify correctly, at the molecular level, the resistance gene. The absence of the amplified B2 haplotype was confirmed, indicating that it has not increased in frequency after its detection in continental Italy around 1985. The B4 haplotype was detected in all populations at the same frequencies as a previous starch gel survey. The possibility that B4 amplification has occurred only once and has migrated across western Mediterranean region is supported by the data. A1 also was detected indirectly by the presence of its closely linked B allele. The B5 haplotype apparently was absent. No amplification at the esterase B locus was detected, except B4, indicating a low rate of occurrence of new amplification at this locus.

Animals↗
PubMed1994

Insecticide susceptibility in mosquitoes (Diptera: Culicidae) from French Polynesia.

Susceptibility to six organophosphate (OP), two pyrethroid (PY), and one carbamate (C) insecticides was investigated in Culex pipiens quinquefasciatus Say, Aedes aegypti (L.), and Aedes polynesiensis Marks larvae from the island of Tahiti. Cx. p. quinquefasciatus and Ae. aegypti were compared with susceptible reference strains treated simultaneously. A low, but significant, resistance to bromophos (4.6x), chlorpyrifos (5.7x), fenthion (2.4x), fenitrothion (5.0x), temephos (4.3x) and permethrin (2.1x) was found in Cx. p. quinquefasciatus, and to malathion (1.5x), temephos (2.3x), permethrin (1.8x) and propoxur (1.7x) in Ae. aegypti. Cx. p. quinquefasciatus was shown to possess over-produced esterases A2 and B2, which are known to be involved in resistance to OPs in other countries. Ae. polynesiensis was less resistant than the Ae. aegypti reference strain to all insecticides except temephos (1.8x) and permethrin (6.7x). To determine whether Ae. polynesiensis had developed resistance to these insecticides in Tahiti, a geographical survey covering 12 islands of the Society, Tuamotu, Tubuai, Marquesas, and Gambier archipelagoes was undertaken with three insecticides (temephos, deltamethrin, and permethrin). Two- to threefold variations in LC50S were observed among collections. Results are discussed in relationship to the level of insecticide exposure on the different islands.

Animals↗
PubMed1994

Functional expression of P-glycoprotein in Saccharomyces cerevisiae confers cellular resistance to the immunosuppressive and antifungal agent FK520.

We have recently reported that expression in yeast cells of P-glycoprotein (P-gp) encoded by the mouse multidrug resistance mdr3 gene (Mdr3) can complement a null ste6 mutation (M. Raymond, P. Gros, M. Whiteway, and D. Y. Thomas, Science 256:232-234, 1992). Here we show that Mdr3 behaves as a fully functional drug transporter in this heterologous expression system. Photolabelling experiments indicate that Mdr3 synthesized in yeast cells binds the drug analog [125I]iodoaryl azidoprazosin, this binding being competed for by vinblastine and tetraphenylphosphonium bromide, two known multidrug resistance drugs. Spheroplasts expressing wild-type Mdr3 (Ser-939) exhibit an ATP-dependent and verapamil-sensitive decreased accumulation of [3H]vinblastine as compared with spheroplasts expressing a mutant form of Mdr3 with impaired transport activity (Phe-939). Expression of Mdr3 in yeast cells can confer resistance to growth inhibition by the antifungal and immunosuppressive agent FK520, suggesting that this compound is a substrate for P-gp in yeast cells. Replacement of Ser-939 in Mdr3 by a series of amino acid substitutions is shown to modulate both the level of cellular resistance to FK520 and the mating efficiency of yeast mdr3 transformants. The effects of these mutations on the function of Mdr3 in yeast cells are similar to those observed in mammalian cells with respect to drug resistance and transport, indicating that transport of a-factor and FK520 in yeast cells is mechanistically similar to drug transport in mammalian cells. The ability of P-gp to confer cellular resistance to FK520 in yeast cells establishes a dominant phenotype that can be assayed for the positive selection of intragenic revertants of P-gp inactive mutants, an important tool for the structure-function analysis of mammalian P-gp in yeast cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Functional expression of P-glycoprotein encoded by the mouse mdr3 gene in yeast cells.

We have expressed P-glycoprotein (P-gp) encoded by the mouse mdr3 gene in the yeast Saccharomyces cerevisiae and have developed an experimental protocol to isolate and purify inside-out plasma membrane vesicles (IOVs) from these cells. Biochemical characterization of IOVs from control and P-gp-expressing cells isolated by this procedure show that they are greatly enriched for plasma membrane markers, are tightly sealed, and are competent for D-glucose transport. P-gp expression in these vesicles results in the appearance of a specific ATP-dependent and temperature-sensitive transport of the drugs colchicine and vinblastine that is osmotically sensitive. P-gp-mediated drug transport into these IOVs is inhibited by a known P-gp modulator, verapamil, and can be abrogated by prior incubation of the IOVs with an anti-P-gp antibody. A Ser-939-->Phe mutation within the predicted transmembrane domain 11 of P-gp, which is known to modulate its function in mammalian cells, drastically reduces drug transport in IOVs obtained from yeast cells expressing the mutant protein. The successful demonstration of active drug transport into IOVs from P-gp-expressing yeast cells indicates that P-gp can mediate both chemotherapeutic drugs and a-pheromone transport in yeast cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

The yeast Candida albicans has a clonal mode of reproduction in a population of infected human immunodeficiency virus-positive patients.

To ascertain the population structure of Candida albicans, we have carried out a multilocus enzyme electrophoresis study based on the analysis of 21 gene loci. We have thus characterized 55 strains isolated one each from 55 human immunodeficiency virus-positive patients. There is considerable polymorphism among the strains. A population-genetic analysis indicates that the two fundamental consequences of sexual reproduction (i.e., segregation and recombination) are apparently absent in this population of C. albicans. The population structure of C. albicans appears to be clonal, a state of affairs that has important medical and biological consequences.

Candida albicans↗
PubMed1993

Transcriptional activation of the mouse mdr3 gene coincides with the appearance of novel transcription initiation sites in multidrug-resistant P388 tumor cells.

In independently derived drug-resistant sublines of the mouse lymphoid tumor P388, multidrug resistance is associated with the exclusive overexpression of the mdr3 gene. In P388/VCR cells, mdr3 overexpression occurs in the absence of gene amplification, while in P388/ADM-2 cells overexpression is associated with mdr3 gene amplification. The mechanism underlying mdr3 overexpression in these cells was investigated. Measurement of the rate of transcription by nuclear "run-on" assays showed that increased mdr3 expression in P388/VCR cells was caused by transcriptional activation of the gene. Analysis of the 5' end of mdr3 mRNA transcripts by primer extension indicated that in P388/VCR cells, these mRNAs extended approximately 200 nucleotides upstream exon 2, about 60 nucleotides longer than their counterparts expressed in normal tissues from the known transcription start site of the gene (TS1). Northern blotting experiments using discrete exon and intron probes derived from the 5' end of the gene near TS1, together with ribonuclease protection using a complementary RNA probe from the same region, demonstrated that transcriptional activation in P388/VCR cells occurred from a novel transcription start site named TS3, located either upstream of TS1 or within intron 1 at a site immediately upstream a novel exon. In P388/ADM-2 cells, Northern blotting and ribonuclease protection identified overexpressed mdr3 mRNAs initiating near TS1 and a large partially spliced mdr3 mRNA species initiating upstream of TS1 at a novel initiation site designated TS2. Therefore, mdr3 overexpression in independently derived multidrug-resistant isolates of P388 cells is associated with the appearance of novel transcription start sites in the gene and novel sequences at the 5' end of the overexpressed mRNAs.

Animals↗
PubMed1993

Trends in neural tube defects 1980-1989.

OBJECTIVES: To determine trends in prevalence of neural tube defects in Australia over the past decade; to investigate the impact of terminations of pregnancy on the birth prevalence of neural tube defects; and to provide a baseline against which to evaluate the potential effects of preventive public health measures. DATA SOURCES: Two population-based registries in Victoria and Western Australia and a statewide survey from Tasmania. DESIGN AND METHOD: A cohort study. Data on the numbers and the prevalence proportions of neural tube defects from three States--Western Australia, Victoria and Tasmania--were compared by Poisson regression. RESULTS: The prevalence proportions for all neural tube defects for all three States remained level over the study period 1980-1989. Terminations of pregnancy for all neural tube defects increased significantly over the decade in all three States. By 1989, 39.9% of all neural tube defects were ascertained as terminations before 20 weeks' gestation, while 10 years previously only 2.9% were. The percentage of cases of anencephaly ascertained as terminations of pregnancy increased from 4.8% in 1980 to 58.6% in 1989. Corresponding figures for spina bifida were 1.4% (1980) and 26.9% (1989), and for encephalocele 0% (1980) and 12.5% (1989). This increase in terminations was associated with a decrease per year in the birth prevalence proportion for anencephaly of 7.0%, for spina bifida of 4%, and for encephalocele of 11.0%, and a reduction in the risk of a birth with a neural tube defect in 1989 of 47% compared with the risk in 1980. CONCLUSION: Complete ascertainment of all terminations for neural tube defects as well as births with neural tube defects is necessary to provide reliable baseline data on the prevalence of neural tube defects. Such data are essential in evaluating primary preventive measures such as the effect of an increase in folic acid intake by women of child-bearing age.

Abortion, Induced↗
PubMed1993

Bioavailability of metformin in tablet form using a new high pressure liquid chromatography assay method.

Twenty-four young healthy volunteers received a single dose of metformin 500 mg (Glucophage, Nordic Laboratories, Canada) in tablet form. Plasma concentrations were determined by HPLC in samples collected prior to and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 15, 18, 24, and 30 h after dosing. Mean (+/- SD) Cmax was 682.1 (160.6) ng ml-1 at a mean (+/- SD) tmax of 2.4 (0.93) h. Overall elimination was monoexponential with a mean (+/- SD) half-life of 3.16 (0.47) h. We conclude that metformin is rapidly absorbed from this formulation and is also rapidly eliminated. Extrapolation to steady state predicts that equilibrium will be reached within 24 h.

Adult↗
PubMed1993

Comparative pharmacokinetics and pharmacodynamics of two marketed bid formulations of diltiazem in healthy volunteers.

Cardizem SR and Bi-Tildiem were both approved in their respective countries on the basis of clinical trials demonstrating efficacy and safety in the treatment of angina pectoris. In this cross-over randomized study, we assessed whether these two sustained-release formulations of diltiazem have equivalent pharmacokinetic and pharmacodynamic profiles. Twenty-four young healthy male volunteers were hooked to Holters and ambulatory blood pressure monitors for 24 h to establish baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), sinus rate and PR intervals. They then received a single dose of 120 mg of diltiazem from one formulation. The pharmacodynamic measurements were recorded for a further 24 h and blood samples were collected over 36 h for evaluation of diltiazem in plasma by a high-performance liquid chromatogrpahic (HPLC) method. The procedures were repeated with the alternate formulation after a 7 d wash-out. Pharmacokinetics showed statistically significant (p < 0.01) differences in AUC0-12 with means (+/- SD) of 519.2(+/- 172.8) and 429.6(+/- 147.2) ng h ml-1, AUC0-36 of 835.6(+/- 281.6) and 730.9 (+/- 271.5) ng h ml-1 and Cmax of 89.1(+/- 30.3) and 61.1(+/- 21.2) ng ml-1 for Cardizem SR and Bi-Tildiem, respectively. The only pharmacodynamic parameter showing a statistically significant difference in change from baseline between the two formulations was DBP with mean (+/- SD) change in AUC0-12 of -13.6(+/- 20.8) and +8.4(+/- 31.7) mm Hg h (p = 0.0135) and in AUC0-24 of -33.0(+/- 43.7) and -0.3(+/- 59.2) mm Hg h (p = 0.0463) for Cardizem SR and Bi-Tildiem, respectively. These findings suggest that assessment of efficacy of sustained-release formulations of diltiazem by bioequivalence could be misleading. They also confirm that a single dose of diltiazem does not elicit a significant pharmacodynamic response in healthy volunteers. Equivalence for such formulations should therefore be demonstrated by pharmacodynamic evaluation or clinical studies in a patient population.

Adult↗
PubMed1993

Mechanisms of insecticide resistance in field populations of Culex pipiens from Italy.

Results of a study on organophosphate (OP) resistance carried out on 4 Italian field populations of Culex pipiens are reported. The A1, A4-B4 and/or A5-B5 nonspecific esterases and insensitive acetylcholinesterase (AChE) were detected in our samples. A2-B2 esterases previously recorded in Italy were not observed. The A4-B4 and/or A5-B5 esterases were first found in Italy where they are at present widespread. Both nonspecific esterases and insensitive AChE are involved in OP resistance, although the high level of OP resistance observed in the Padova population could be correlated with both a high frequency of insensitive AChE and A5-B5 esterases.

Acetylcholinesterase↗
PubMed1992

Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr gene.

Multidrug resistance in mammalian tumor cells is associated with the overexpression of mdr genes encoding P-glycoproteins, which function as drug efflux pumps. A yeast homolog of mdr, STE6, mediates export of a-factor mating peptide. Yeast MATa cells carrying a ste6 deletion produce no extracellular a-factor and therefore are defective in mating. Expression of a complementary DNA for the mouse mdr3 gene in a yeast ste6 deletion strain restored ability to export a-factor and to mate. A mutation (a serine to phenylalanine substitution at amino acid 939) known to affect the activity of the mdr3 gene product abolished its ability to complement the yeast ste6 deletion. Thus, functions of P-glycoproteins in normal mammalian cells may include the transmembrane export of endogenous peptides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Disc and field damage in patients with unilateral visual field loss from primary open-angle glaucoma.

To assess the temporal relationship between field and disc change in early glaucoma, 24 patients with unilateral visual field loss from primary open angle glaucoma were identified for planimetric optic disc measurements. Cross-sectional analysis of disc rim area was performed and compared to 25 age-matched normal controls. The mean (+/- SD) disc rim area in eyes with normal visual fields (1.10 +/- 0.31 mm2) was slightly larger than that of eyes with visual field loss (0.90 +/- 0.33 mm2). The mean disc rim area in the control group (1.49 +/- 0.19 mm2) was significantly different from both sets of eyes in the asymmetric primary open angle glaucoma patients (p = 0.000). These findings support the hypothesis that loss of the optic disc rim can be detected before perimetric abnormalities develop in patients with glaucoma.

Aged↗
PubMed1992

Identification of two distinct amplifications of the esterase B locus in Culex pipiens (L.) mosquitoes from Mediterranean countries.

Two new highly active esterases were detected by starch electrophoretic studies in Culex pipiens mosquitoes from the area of Montpellier (France) and from Cyprus. We demonstrate here that both the French and the Cyprus esterases B are overproduced due to amplification of the coding gene. The production of the esterase B is approximately 50- and 500-fold higher in mosquitoes from France and Cyprus, respectively, than in susceptible insects, whereas the number of gene copies is about 25 and 250. Differences of about 7- and 95-fold were also found in the degree of chlorpyrifos resistance. RFLP comparison of the amplified region containing the esterase B gene revealed large differences between French and Cyprus mosquitoes. It thus appears that two distinct haplotypes with an esterase B gene coding an enzyme with identical electrophoretic mobility have been amplified. We therefore named the haplotypes in mosquitoes from France and Cyprus B4 and B5, respectively. The estimated genetic distance between these two haplotypes is not smaller than those observed in all pair comparisons of other known esterase B haplotypes. These results are discussed in the context of amplification phenomena.

Animals↗
PubMed1991

Simultaneous identification of eight leucocyte subsets of human peripheral blood using three-colour immunofluorescence flow cytometric analysis.

The full analytical potential of flow cytometry has been exploited in order to identify a maximum of human peripheral blood leucocyte subsets in a single tube. For this purpose a mixture composed of six different monoclonal antibodies directly coupled to FITC or phycoerythrin or indirectly linked to the DuoChrome reagent via the biotin/streptavidin system was used. This combination of monoclonal antibodies and fluorochromes offered the possibility of simultaneously determining eight leucocyte subsets of human peripheral blood using a single laser beam. These subsets were T4 cells, bright and dim T8 cells, T null (CD3+ CD4- CD8-) cells, NK cells and B cells, polymorphonuclear cells and monocytes. This method is very easy to perform, can be applied to samples from other lymphoid tissues such as tonsils and is particularly useful when starting with a low number of cells.

Antigens, CD↗
PubMed1991

Worldwide migration of amplified insecticide resistance genes in mosquitoes.

In Culex pipiens, overproduction of nonspecific esterases is a common mechanism of resistance to organophosphate insecticides. The esterases are attributed to closely linked loci named A and B according to substrate preference, and overproduction of all esterases B is due to gene amplification. Distribution of electrophoretically distinct variants of overproduced esterases A and B is geographically restricted, with the exception of esterases A2 and B2, always found together throughout at least three continents. To determine whether this situation is due to migration or to a high mutation rate, esterase B structural genes and their flanking regions were compared by sequence and/or restriction fragment length polymorphism analysis. Whereas structural genes were similar, flanking regions of electrophoretically dissimilar esterases B varied considerably. In contrast, flanking sequences of esterases B2 from different geographical locations (Africa, Asia, North America) were identical. These results suggest that amplified esterase B2 genes originated from an initial event that has subsequently spread organophosphate insecticide resistance by migration.

Amino Acid Sequence↗
PubMed1990

Cell-specific activity of cis-acting regulatory elements in the promoter of the mouse multidrug resistance gene mdr1.

To define cis-acting elements implicated in transcriptional regulation of the mouse multidrug resistance gene mdr1, we have cloned and characterized the 5' end of the gene. Nucleotide sequence analysis identified TATA, GGGCGG, and CCAAT consensus sequence elements at positions -27, -47, and -83, respectively. The transcriptional activities of 5' deletion fragments from the promoter linked to a reporter gene were tested in mouse cell lines of different tissue origins shown to express different levels of endogenous mdr1 RNA. Sequences located between nucleotides -93 and +84 were able to confer basal promoter activity and cell specificity to the reporter gene. The addition to the basal promoter of sequences upstream of position -141 was found to up or down regulate the basal level of expression of the reporter gene in a cell-specific manner.

Animals↗