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Biomedical subjects

B Fournier

Publications and source records attributed to B Fournier.

At least 91 records · Page 5Linked to original sources

Point mutation in the pribnow box, the molecular basis of beta-lactamase overproduction in Klebsiella oxytoca.

Klebsiella oxytoca mutants resistant to a variety of beta-lactams were obtained in vitro on aztreonam. Constitutive beta-lactamase production was much higher in the mutants than in the susceptible strains (75-fold). The only difference observed in these mutants compared with the susceptible strains were point mutations in the Pribnow box: a transversion (G-->T) in the first base for one mutant or a transition (G-->A) in the fifth base of the -10 consensus sequence for the other three mutants. The transcriptional output of the beta-lactamase gene (blaOXY) from the mutants was significantly higher than that of the blaOXY gene from the susceptible strains.

Anti-Bacterial Agents↗

Reference limits of apolipoprotein A-I and apolipoprotein B using an IFCC standardized immunonephelometric method.

An important collaborative study organized by the IFCC enabled the selection of international reference materials and the standardization of commercially available methods by the use of common calibrators. In this paper, we report the reference limits of apolipoprotein A-I and apolipoprotein B in a selected healthy French population. The apolipoprotein measurements were performed on BNA Behring using reagents and protocols supplied by the manufacturer: the standard sera were calibrated using the IFCC-WHO reference preparations (SP1 and SP3). In addition, the apolipoprotein B protocol was modified by the addition of a supplementary reagent to reduce the interference by lipaemic samples on immunonephelometric measurement. In a sample of 115 random serum samples, there was a decrease in mean concentration between non-standardized and standardized methods: -4.8% for apolipoprotein A-I and -4.7% for apolipoprotein B. The reference limits for apolipoprotein A-I are unaffected by gender between 4 and 14 years, thereafter vary with age and gender until 40 years and with gender alone between 40 and 60 years. For apolipoprotein B, the variation with gender is only significant between 30 and 49 years.

Adolescent↗

Stress fractures of the heads of the metatarsals. A new cause of metatarsal pain.

We report 16 cases of epiphyseal metatarsal stress fractures in 11 patients. Four patients had osteoporosis and two of these four were under fluoride therapy. Three of the fractures occurred upon resumption of weight-bearing. The fractures were distributed over the five rays; seven fractures were located to the second metatarsal. Manifestations were acute focal metatarsal pain, diffuse edema of the forefoot and inflammatory metatarsophalangeal arthropathy. Delayed, transient visualization of a linear area of epiphyseal sclerosis occurred in 14 cases. Radionuclide bone scans consistently showed early accumulation of the tracer in the metatarsal head. The focus of increased activity extended to the shaft in three cases. The main differential diagnoses are second ray syndrome, metatarsophalangeal arthritis, focal radial reflex sympathetic dystrophy of the foot and osteonecrosis of the metatarsal heads. The clinical and roentgenographic outcome was consistently favorable after one month without weight-bearing. These fractures can simulate, complicate, induce (two cases), reflex sympathetic dystrophy of the foot or occur concomitantly with (two cases).

Aged↗

[Changes in the cardiovascular risk indicators in adolescents between 1980 and 1991].

The aim of this study was to evaluate the trends of indicators of cardiovascular risk (smoking, physical activity, cholesterol, triglycerides...) in adolescents between 14 and 18 years of age. The data was recensed at the Centre of Preventive Medicine of Vandoeuvre-lès-Nancy which was responsible for periodic Social Security health check-ups in 6,974 adolescents in 1980, 1984, 1988 and 1991. The analysis of the trends of the indicators of cardiovascular risk took into consideration the socio-economic changes of the population recruited during this period and the long-term analytical variations of biochemical parameters. Globally, between 1980 and 1991, there was a decrease in the percentage of smokers (21.8% to 13.5%) which was more marked in boys than in girls, an increase in physical activities (46.9% to 57.5%), a linear reduction in serum cholesterol (4.65 mmol/l to 4.33 mmol/l in boys, and 4.94 mmol/l to 4.72 mmol/l in girls), and no significant changes in serum triglycerides. These results confirm those reported by others and are encouraging for cardiovascular disease prevention and should be confirmed in adults groups.

Adolescent↗

[Reference values of lipoprotein(a) in a French population].

OBJECTIVES: The aim of this work is to study the effect of different biological factors that could affect Lp(a) level in a presumably healthy population and to establish reference limits. METHODS: We selected 723 subjects (367 men and 356 women) for the age interval 4 to 64 years for evaluation. RESULTS: The distribution of Lp(a) is not Gaussian; 50.5% of subjects had Lp(a) concentrations under 0.10 g/l and the value for the 75th percentile was 0.27 g/l and 0.57 g/l for the 90th percentile. No relationship was observed between Lp(a) concentration and cholesterolaemia, triglyceridaemia, glycaemia, inflammatory proteins (orosomucoide and CRP), overweight, tobacco consumption and oral contraceptive use. The menopause state in women was a factor correlated with increased Lp(a) but this increase was not significant. Moreover, alcohol consumption (more than 44 g per day in men and more than 22 g per day in women) was associated with lower Lp(a) values. Among familial cardiovascular risks, only paternal listing of hypertension was associated with Lp(a) concentration in men. CONCLUSION: The measurement of Lp(a) in a young subject could be used as a genetic marker of cardiovascular risk associated with abnormal lipid metabolism and thrombosis phenomena.

Adolescent↗

Isolation and expression of a cDNA encoding the precursor for a novel member (ACADSB) of the acyl-CoA dehydrogenase gene family.

The acyl-CoA dehydrogenases (ACDs) are a family of mitochondrial enzymes that oxidize straight chain or branched chain acyl-CoAs in the metabolism of fatty acids or branched chain amino acids. Deficiencies in members of this gene family are important causes of human disease. A cDNA encoding the human precursor for a novel member (gene symbol ACADSB) of the ACD gene family has been isolated and characterized. The open reading frame of 1.3 kb encodes a precursor protein of 431 amino acids, which is processed in vitro to yield a mature protein of 399 amino acids. The cDNA has significant sequence similarity to other members of the acyl-CoA dehydrogenase family, with the greatest homology (38%) to the short chain acyl-CoA dehydrogenase. The cDNA was expressed in eukaryotic (COS) and prokaryotic (Escherichia coli) cells, producing a protein of the expected size, with activity toward the short branched chain acyl-CoA derivatives ((S)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2-methylhexanoyl-CoA), as well as toward the short straight chain acyl-CoAs (butyryl-CoA and hexanoyl-CoA).

Acyl-CoA Dehydrogenase↗

Klebsiella oxytoca: resistance to aztreonam by overproduction of the chromosomally encoded beta-lactamase.

Aztreonam-resistant Klebsiella oxytoca strain SL7811 was selected on agar containing 1 microgram of aztreonam per ml from a susceptible strain SL781. The MICs for the resistant mutant towards penicillins, aztreonam and ceftriaxone were much higher, to cefotaxime slightly higher and to ceftazidime unchanged. Synthesis of beta-lactamase was 223-fold greater in the mutant compared with the susceptible strain. SL781 and its resistant mutant SL7811 produced beta-lactamase with the same isoelectric point and substrate profile. The beta-lactamase genes from SL781 and SL7811 were cloned in plasmid pBGS18 giving pBOF-1 and pBOF-4 respectively. The sequences of the two putative promoters indicated two modifications in the resistant plasmid pBOF-4: a transversion (G-->T) in the first base of the -10 consensus sequence and a deletion of one C residue four base pairs upstream of the -10 hexamer.

Amino Acid Sequence↗

Effects of two neuronal antidiuretic molecules, neuroparsin and 5-hydroxytryptamine, on cytosolic free calcium monitored with indo-1 in epithelial and muscular cells of the African locust rectum.

Using the probe indo-1 in a microspectrofluorimetric study, it was demonstrated that the locust antidiuretic neurohormone, neuroparsin, enhanced cytosolic free Ca2+ concentrations, measured as percentages of the ratio F405/F480 (R), in epithelial cells of the African locust rectum. 5-hydroxytryptamine, whose antidiuretic effect was previously established, enhanced R in longitudinal muscular cells, and was able to increase R slightly in epithelial cells. The possibility of reciprocal Ca2+ movements between muscular and epithelial cells is discussed. Both of the neuronal molecules, which act via distinct transduction pathways (phosphoinositide turnover for neuroparsin, and Ca(2+)-dependent adenylate cyclase for 5-hydroxytryptamine), stimulated an increase in R by causing Ca2+ entry through dihydropyridine-sensitive Ca2+ channels. Cyclic nucleotides (cAMP and cGMP) lowered R in epithelial cells, the cGMP effect being interpreted as a feedback control on phosphoinositide turnover and resulting in the ability to re-establish cAMP production to levels incompatible with high PLC activity. In longitudinal muscular cells, the increase in R due to cAMP suggests the involvement of 5-hydroxytryptamine in stimulation of adenylate cyclase activity. Furthermore, results enabled the localization in epithelial cells of the transduction pathways mediating the actions of another antidiuretic factor extracted from the glandular lobes of the locust corpora cardiaca.

Animals↗

Peroxisomal disorders: a review.

Until recently peroxisomal disorders were considered to be extremely rare and the diagnostic procedures available for postanatal and prenatal diagnosis were not widely known. At present, 17 human disorders are linked to peroxisomal dysfunction. The clinical, biochemical and morphological peroxisome heterogeneity described in the different diseases illustrate that only combined analysis of all the different approaches will lead to a correct diagnosis and a coherent pathophysiological model to guide ongoing research. With the study of human peroxisomal disease, advances have been gained as to the function of the peroxisome in normal and pathological conditions. Genetic analysis of peroxisome biogenesis and research on peroxisomal targeting signals are now in progress. Peroxisomal disorders are usually classified according to the degree of biochemical impairment. In this paper, a tentative classification of peroxisomal disorders will be proposed, based on the degree of biochemical abnormalities combined with new data obtained on whether or not defective peroxisome assembly is involved: (1) disorders with peroxisome assembly deficiencies; (2) disorders with single enzyme deficiencies. The clinical onset and the major symptoms of the various disorders, and the recently discovered findings are discussed.

Biological Transport↗

Reticulocytes: biological variations and reference limits.

The reticulocyte count is a good index of erythropoietic activity. Automated methods, mainly flow cytometry, have made the counting easier, more accurate and reproducible. The data presented describe the counting of reticulocytes in 1219 apparently healthy subjects of both sexes who came for a periodic health examination. Their ages varied from 4 to over 60 years. The reticulocytes were counted with a flow cytometer (Sysmex R-3000) with Auramine-O as fluorochrome. There was no statistical difference between boys and girls aged 4-19 years. However, the reticulocyte count was significantly higher in men than in women over 20 years of age. The reticulocyte count was affected neither by the menstrual cycle in girls at puberty, nor by oral contraceptives and the menopause in women. No effect of moderate smoking was observed in either sex. Reference limits of the reticulocyte counts (percentage and absolute value) according to age and sex and the three types of reticulocytes are provided.

Adolescent↗

Large deletion of the peroxisomal acyl-CoA oxidase gene in pseudoneonatal adrenoleukodystrophy.

We have cloned the cDNA encoding human peroxisomal acyl-CoA oxidase, the first enzyme in the peroxisomal beta-oxidation of very long chain fatty acids. Its nucleotide sequence was found to be highly homologous (85%) to the rat cDNA counterpart. An 88% homology between rat and human was found in the COOH-terminal end of the cDNA which includes the Ser-Lys-Leu peroxisomal targeting signal common to many peroxisomal proteins. The gene spans approximately 30-40 kb and is poorly polymorphic. Southern blot analyses were performed in two previously reported siblings with an isolated peroxisomal acyl-CoA oxidase deficiency (pseudoneonatal adrenoleukodystrophy). A deletion of at least 17 kb, starting down-stream from exon 2 and extending beyond the 3' end of the gene, was observed in the two patients. These observations provide a molecular basis for the observed acyl-CoA oxidase deficiency in our family. In addition, our study will enable the characterization of the genetic defect in unrelated families with suspected acyl-CoA oxidase disorders.

Acyl-CoA Oxidase↗

Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer.

Prospective morbidity and mortality rates associated with resection of lung cancer that are reflective of the current trend toward preoperative therapy are not readily available in the current literature. To determine their prevalence, we prospectively analyzed the results of 783 resections performed within contributing Lung Cancer Study Group (LCSG) centers. There were 543 men and 240 women with a mean age of 63.44 years. Of the 783 resections, there were 411 lobectomies, 135 pneumonectomies, and 237 other procedures. Thirty patients died postoperatively (mortality, 3.8%) and 211 had a major complication (27%). Complications occurred more commonly in men (34.3%, p = 0.001), in patients age 60 or older (34.0%, p = 0.001), and in patients with a Karnofsky index < 9 (44%, p < 0.001). There was no significant difference between mortality, significant morbidity rates for lobectomy (28.2%), and pneumonectomy (31.9%), or for simple (28.3%) and extended resection (31.9%). The seemingly higher incidence of major postoperative events reported in this series not only reflects the prospective nature of this analysis but also the fact that over 25% of patients were in other therapeutic trials involving neoadjuvant or postoperative adjuvant regimens. Within that context, these data appear to be a reasonable estimate of modern surgical morbidity rates in the treatment of lung cancer.

Aged↗

Systemic and regional haemodynamic effects of 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) and alpha-methyl-5-HT, in the anaesthetised rat.

The present experiment was performed to investigate the haemodynamic effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) in the anaesthetised normotensive rat. DOI (1-300 micrograms/kg i.v.) increased mean arterial pressure (MAP), total peripheral resistance (TPR) and decreased cardiac output (CO) and heart rate (HR). DOI increased all vascular resistances investigated (hindquarters, mesenteric and renal). Alpha-methyl-5-HT (10-300 micrograms/kg i.v.) dose-dependently increased MAP, TPR, all regional vascular resistances and decreased CO and HR. The bradycardia induced by alpha-methyl-5-HT was suppressed by bivagotomy. Both DOI and alpha-methyl-5-HT were more effective on renal vascular bed than hindquarters and mesenteric vascular beds. The effects of DOI and alpha-methyl-5-HT were antagonised by spiperone (10 or 100 micrograms/kg i.v.) and LY 53857 (10 micrograms/kg i.v.). Intracerebroventricular administration of DOI (100 micrograms/kg) increased MAP, TPR, regional vascular resistances and did not change HR and CO. Pretreatment with xylamidine (10 micrograms/kg i.v.), a selective peripheral 5-HT2 receptor antagonist, blocked i.v. and i.c.v. effects of DOI. These results suggest that: 1) the increase in MAP induced by DOI and alpha-methyl-5-HT is due to an increase in TPR. All regional vascular beds and in particular the renal vascular bed participate in the increase of TPR. 2) Peripheral--and may be--central 5-HT2 receptors seem to be implicated in the control of regional vascular resistances. 3) Cardiac effects of alpha-methyl-5-HT are baroreflexly-mediated whereas those of DOI are--at least in part--centrally mediated.

Amphetamines↗

Vascular and cardiac effects of alpha-methyl-5-HT and DOI are mediated by different 5-HT receptors in the pithed rat.

In pithed rats, alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) increased blood pressure and heart rate, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) almost exclusively increased blood pressure and 1-(3-chlorophenyl)piperazine (mCPP), heart rate. The maximal responses relative to 5-HT indicate that alpha-methyl-5-HT may be a full agonist at vascular and cardiac 5-HT receptors, DOI a partial agonist at both receptors and mCPP a full agonist at cardiac 5-HT receptors but a partial agonist at vascular 5-HT receptors. The alpha 1-adrenoceptor antagonist, 2-[2-[4(o-methoxyphenyl)-piperazine-1-yl]-ethyl]4,4-dimethyl -1,3(2H-4H) isoquinolinedione (AR-C 239), did not change the pressor and tachycardiac effects of alpha-methyl-5-HT and DOI, excluding the participation of alpha 1-adrenoceptors. 4-Isopropyl-7-methyl-9-(2-hydroxy-1-methylpropoxycarbonyl) 4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline (LY 53857), spiperone and ketanserin but not propranolol antagonised the pressor effect of alpha-methyl-5-HT, indicating a preferential participation of 5-HT2 receptors although an implication of 5-HT1C receptors could not be ruled out. Spiperone, spiperone plus propranolol, LY 53857, ketanserin and propranolol antagonised the pressor effects of DOI suggesting the stimulation of both 5-HT2 and 5-HT1C receptors. Propranolol and spiperone plus propranolol suppressed the weak increase in heart rate induced by DOI, indicating the stimulation of 5-HT1C receptors. However, propranolol and LY 53857 only antagonised the tachycardiac effects of a high dose of alpha-methyl-5-HT. We hypothesised that the pressor and tachycardiac effects of these agonists may be mediated by 5-HT2 and 5-HT1C receptors, respectively. However, the availability of specific 5-HT1C and/or 5-HT2 receptor antagonists is necessary to verify our hypothesis and before a clear-cut conclusion can be drawn.

Adrenergic alpha-Antagonists↗