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Biomedical subjects

A Favier

Publications and source records attributed to A Favier.

At least 55 records · Page 3Linked to original sources
PubMed2001

Evidence for a dimerisation state of the Bacillus subtilis catabolite repression HPr-like protein, Crh.

The Bacillus subtilis catabolite repression HPr (Crh) exhibits 45% sequence identity when compared to histidine-containing protein (HPr), a phosphocarrier protein of the phosphoenolpyruvate:carbohydrate phosphotransferase system. We report here that Crh preparations contain a mixture of monomers and homodimers, whereas HPr is known to be monomeric in solution. The dissociation rate of dimers is very slow (t1/2 of about 10 hours), and the percentage of dimers in Crh preparations increases with rising temperature or protein concentration. However, at temperatures above 25 degrees C and a protein concentration of 10 mg/ml, Crh dimers slowly aggregate. Typically, NMR spectra recorded at 25 degrees C showed the coexistence of both forms of Crh, while in Crh solutions kept at 35 degrees C, almost exclusively Crh monomers could be detected. Circular dichroism analysis revealed that the monomeric and dimeric forms of Crh are well folded and exhibit the same overall structure. The physiological significance of the slow Crh monomer/dimer equilibrium remains enigmatic.

Bacillus subtilis↗
PubMed2001

Effect of two years' supplementation with natural antioxidants on vitamin and trace element status biomarkers: preliminary data of the SU.VI.MAX study.

The "SUpplementation en VItamines et Minéraux AntioXidants" (SU.VI.MAX) study is a randomized double-blind, placebo controlled, primary-prevention trial designed to test the efficacy of a daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 microg; and zinc, 20 mg) at nutritional doses (one to three times the daily recommended dietary allowances), in reducing the frequency of cancers and cardiovascular diseases. The study involves 12,735 eligible subjects (women aged 35-60 years, men aged 45-60 years) included in 1994 in France. They will be followed up for 8 years. The targeted population is the general population. The aim of this specific analysis is to assess the effect of 2 years of supplementation on biochemical indicators of vitamin and trace element on a subsample of 1000 subjects. The mean (+/- standard deviation) concentrations of plasma beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc among participants who were randomly assigned to receive a daily supplementation with beta-carotene, vitamin E, vitamin C, selenium and zinc for 2 years were significantly higher than those who were assigned to receive placebo. Specifically, the mean concentrations among men in the intervention group were 0.86 +/- 0.70 micromol/L for beta-carotene, 35.3 +/- 9.3 micromol/L for alpha-tocopherol, 11.5 +/- 4.7 microg/ mL for vitamin C, 1.65 +/- 0.33 micromol/L for selenium, and 16.2 +/- 3.9 micromol/L for zinc. The mean concentrations among women in the intervention were 1.25 +/- 0.90 micromol/L for beta-carotene, 34.9 +/- 8.4 micromol/L for alpha-tocopherol, 12.6 +/- 4.0 microg/mL for vitamin C, 1.68 +/- 0.37 micromol/L for selenium, and 15.3 +/- 3.9 micromol/L for zinc. The values observed for beta-carotene and vitamin E in the supplementation group after 2 years of intervention are those that have been associated with the lowest risk of cancer in observational studies. They are definitely lower than concentrations reported in intervention studies showing an apparent negative effect of high levels of beta-carotene supplementation on the lung cancer incidence rate in high-risk subjects (initial level multiplied by 12-18). Data from the follow-up will ascertain if any plausible reduction in the incidence rate of cancers may be associated with such amounts of antioxidant agents.

Adult↗
PubMed2001

[Glucose and redox sensitive transcription factors: consequences on the insulin receptor].

During diabetes an oxidizing stress can be observed, whose origins are multiple. This stress can be regarded as a particular messenger, certainly modifying the transduction of the insulinic signal but also the activity of certain transcription factors. Indeed NF-kappa B activity is increased, while Sp1 activity drops in this context. NF-kappa B activation takes certainly part in vascular remodeling and plays a role in the genesis of the oxidative stress. Hence, NF-kappa B activity precociously increases in the states of insulin resistance before hyperglycemia sets in. Sp1 undergoes a significant fall in activity in the presence of glucose. This activity can be restored by antioxydants in the cell culture medium, Sp1 being necessary to insulin receptor expression, the question arises whether this drop in activity modifies significantly the insulin expression.

Arteriosclerosis↗
PubMed2000

Prion infection impairs the cellular response to oxidative stress.

The molecular mechanism of neurodegeneration in transmissible spongiform encephalopathies remains uncertain. In this study, it was demonstrated that prion-infected hypothalamic neuronal GT1 cells displayed a higher sensitivity to induced oxidative stress over noninfected cells. In addition, the infected cells presented an increased lipid peroxidation and signs of apoptosis associated with a dramatic reduction in the activities of the glutathione-dependent and superoxide dismutase antioxidant systems. This study indicates for the first time that prion infection results in an alteration of the molecular mechanisms promoting cellular resistance to reactive oxygen species. This finding is vital for future therapeutic approaches in transmissible spongiform encephalopathies and the understanding of the function of the prion protein.

Blotting, Western↗
PubMed2000

Mobile-phase-viscosity dependence on DNA separation in slalom chromatography.

Slalom chromatography (SC) is an alternative chromatographic procedure for the separation of relatively large double-stranded DNA molecules and is based on a new principle. The retardation of the DNA fragments from the cleavage of the Lambda DNA by the KpnI restriction enzyme was studied using an acetonitrile-phosphate buffer as a mobile phase with various concentrations of viscosity modifier (i.e. glycerol) and a C1 column as a stationary phase. The DNA molecule retention was accurately described over the glycerol concentration range using a model previously established. It was shown that the eluent viscosity increase enhanced the slalom chromatographic capacity to separate the DNA fragments. A connection between SC and 'hydrodynamic chromatography' processes was predicted to link the two processes in a global separation mechanism based on a non-equilibrium principle.

Chromatography, Liquid↗
PubMed2000

Selenium determination in human plasma lipoprotein fractions by mass spectrometry analysis.

Previous observations have suggested that lipoproteins may be involved in the transport of selenium in humans. To further investigate this question, selenium was measured in lipoprotein fractions isolated from plasma of healthy adults. A gas chromatographic-mass spectrometric method using the isotopic dilution technique was developed to ensure a reliable measurement of low amounts of selenium. About 3% of total plasma selenium was bound to lipoproteins, mainly to the LDL fraction. After solvent fractionation of LDL and HDL, the major part of the selenium was recovered in the protein extract, suggesting that it may be incorporated in apolipoproteins. The exact form of Se is not yet clearly established. Considering the different Se compounds found in proteins, it is postulated to be selenomethionine, and/or participating in a selenium-sulphur bond. This could explain why the amount of selenium bound to apolipoprotein B in LDL was about twice that which could be expected from a random substitution of selenomethionine for methionine.

Adult↗
PubMed2000

Mechanism of DNA hydrodynamic separation in chromatography.

An alternative chromatographic procedure for the separation of large double-stranded DNA molecules was discovered recently and called "slalom chromatography". This fractionation is based on a new hydrodynamic process that is determined by the progression of the mobile-phase flow through the interstitial spaces created between the highly packed particles inside the column. Here, the separation is treated as the result of a slowing down of the large double-stranded DNA fragments in relation to their size with the flow direction changing around the particles. A model, based on the concept derived from the reorientation time of macromolecules, was adequate to describe the hydrodynamic phenomenon. This model constitutes an attractive tool to enhance the expansion of this chromatographic procedure and provide valuable information on the dynamic behavior of biological polymers.

Bacteriophage lambda↗
PubMed2000

Determination of salicylate hydroxylation products as an in vivo oxidative stress marker.

The in vivo measurement of highly reactive free radicals, such as the z.rad OH radical, is very difficult. New specific markers, which are based on the ability of z.rad OH to attack the benzene rings of aromatic molecules, are currently under investigation. The produced hydroxylated compounds can be measured directly. In vivo, radical metabolism of salicylic acid produces two main hydroxylated derivatives (2,3- and 2,5-dihydroxybenzoic acids). The latter acid can be also produced by enzymatic pathways through the cytochrome P-450 system, while the former acid is reported to be solely formed by direct hydroxyl radical attack. Therefore, measurement of 2, 3-DHBA, following oral administration of the drug acetyl salicylate, could be proposed for assessment of oxidative stress in vivo. In this paper, a sensitive method for the identification and quantification of hydroxylation products from the reaction of z. rad OH with salicylate in vivo is presented. It employs a high performance liquid chromatography and electrochemical detection system. A detection limit of < 1 pmol for the hydroxylation products has been achieved with linear response over at least five orders of magnitude. Using this technique, we measured plasma levels of 2,3- and 2,5-DHBA dihydroxylated derivatives and salicylic acid and determined the ratios following administration of 1 g acetyl salicylate in 20 healthy subjects.

Adult↗
PubMed2000

Vitamin and nutritional status in Cuban smokers and nonsmokers in the context of an emerging epidemic neuropathy.

A prospective survey was conducted in a random sample of smokers (SMO) and non-smokers (NON) men living in Havana. The aim of the survey was to investigate metabolic and dietary parameters discriminating between SMO and NON volunteers, which could explain underlying mechanisms to the higher risk of Epidemic Neuropathy (51,000 reported cases in Cuba from late 1991) previously demonstrated in the Cuban smoker. Forty three blood markers were determined and dietary intakes evaluated during 4 seasonal periods. alpha-carotene, beta-carotene, beta-cryptoxanthin, total carotenoids and riboflavin blood concentrations were lower in SMO vs. NON subjects. Activities of glutathione reductase and butryrylcholinesterase were lower in the SMO group, as did total protein levels. Copper and thiocyanates were higher in SMO subjects. Most of the dietary parameters did not differ between the two groups of volunteers. Low biologically available quantities of carotenoids and riboflavin from low dietary intakes and depletion through smoking would be the main precipitating factors of Epidemic Neuropathy. Protein depletion and copper delivery via tobacco smoke, sunlight exposure, level of physical activity and high consumption of cigarettes, in a context of low dietary supplies concerning especially B vitamins, were probably aggravating factors through oxidative stress and impairment of cyanide detoxification.

Adult↗
PubMed2000

Effect of a synthetic lipid immunomodulator on the regulation of the transcription factor NF-kappaB.

Macrophage activation plays a central role in host defense against a variety of pathogens via inducible messengers. The transcription factor NF-kappaB controls the synthesis of cytokines involved in immune responses. In quiescent cells, NF-kappaB is located in the cytosol bound to an inhibitor IkappaB. Upon appropriate signal, NF-KB translocates to the nucleus and binds to DNA. The present study investigated the involvement of an immunomodulator, (diHDA-glycerol) on the NF-kappaB/IkappaB complex. Results were compared to those obtained with lipopolysaccharide (LPS) as a major virulence factor in bacterial sepsis. Data showed that exposure of J774.1 cells either to LPS or diHDA-glycerol substantially increased with time the nuclear levels of NF-kappaB complexes. Antibodies to various NF-kappaB proteins supershifted p50, p65 and to a lesser extent c-rel. Western blot analyses showed a rapid cytosolic IkappaB-alpha turn over following LPS exposure in contrast to diHDA-glycerol treatment. Further experiments investigated the involvement of protein kinase C (PKC) by using two inhibitors, staurosporine and H7. Pretreatment of J774.1 with either inhibitor prior to diHDA-glycerol or LPS exposure decreased NF-kappaB activation. Our results indicate that diHDA-glycerol was acting on NF-kappaB through IkappaB regulative mechanisms differing from those used by LPS. DiHDA-glycerol is likely acting on many other transcription factors targeting distinct genes implied in up regulation of the immune system.

Adjuvants, Immunologic↗
PubMed1999

The interactions of substituted pyrido[1,2-e]purines with oligonucleotides depend on the amphiphilic properties of their side chain.

Three pyrido[1,2-e]purines of increasing hydrophilicity have been synthesized to evaluate as anticancer agents. These drugs interact quite differently with a synthetic oligodeoxynucleotide d(CGATCG)2. [1] is very hydrophobic due to a phenyl residue in its side chain. It only shows limited interactions with the minihelix without any evidence of intercalation. [2] and [3], on the other hand, have one ([2]) or two ([3]) hydroxyl groups in their acyl chain and present rather amphiphilic properties. The result is a similar intercalation of these derivatives between C and G base pairs as revealed by intermolecular nOe, 1H and 31P chemical shift variations. Models for the intercalation of [2] are proposed using energy minimizations and molecular dynamics (MD) calculations subject to restraints from nOe connectivities. Simulations and experiments indicate weak stability and thus fast exchange of [2] in its intercalation site.

Animals↗
PubMed1999

Gas chromatographic-mass spectrometric determination of total homocysteine in human plasma by stable isotope dilution: method and clinical applications.

The detection and quantitation of slight increases of plasma homocysteine levels is of growing interest. This has prompted us to develop a highly sensitive and accurate capillary gas chromatography-mass spectrometry (GC-MS) method. The method proved to be highly sensitive (DL=0.17 micromol/l) with between- and within-run precision less than 6% and 7%, respectively. Reference values of plasma total homocysteine have been determined for men (n=39) and women (n=36), showing a significant difference (P=0.003) between gender. Preliminary results in cerebrovascular accidents and in venous thrombosis are presented.

Adult↗
PubMed1999

The human immunodeficiency virus-1 Tat protein increases cell proliferation, alters sensitivity to zinc chelator-induced apoptosis, and changes Sp1 DNA binding in HeLa cells.

The HIV-1 transcriptional regulatory protein Tat is a pleiotropic factor that represses expression of the human Mn-superoxide dismutase. Tat increases oxidative stress, as shown by decreased glutathione and NADPH levels. These redox changes enhance proliferation and apoptosis and alter the activity of zinc thiolate-containing proteins such as Sp1. Cells stably producing the Tat protein have an increased proliferation rate, which can be inhibited by pretreatment with the antioxidant mercaptopropionylglycine. Conversely, cells exposed to low concentrations of the oxidant paraquat are stimulated to divide. Intermediate and higher paraquat levels result in increased apoptosis or necrosis, respectively, suggesting that the physiological end point depends on the dose of oxidant used. Furthermore, treatment with the zinc chelator (N,N,N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) sensitizes HeLa-tat cells to apoptosis. In these cells, binding of the zinc-containing factor Sp1 to its DNA sequence is higher than in parental cells. Normal DNA binding is partially restored by pretreatment with a compound that mimics superoxide dismutase activity. Interestingly, Sp1-DNA interactions decrease more rapidly in the HeLa-tat cells after TPEN treatment. HeLa cell extracts incubated in the presence of purified Tat protein have increased Sp1 binding, consistent with the results observed in Tat-transfected cells. These results suggest that the Tat protein, via direct or indirect mechanisms, increases proliferation, sensitizes cells to apoptosis, and changes the conformation of Sp1, affecting its ability to bind to its cognate DNA sequence and to retain its zinc.

Apoptosis↗
PubMed1999

Impairment of cultured cell proliferation and metallothionein expression by metal chelator NNN'N'-tetrakis-(2-pyridylmethyl)ethylene diamine.

Metallothioneins (MT) are a family of intracellular, cysteine-rich, zinc-binding proteins. Their expression is constitutive but can also be induced at the transcriptional level by various stimuli. In this study, we exposed HaCaT human keratinocytes to excess zinc (ZnCl2) or to zinc deprivation by the diffusible chelator NNN'N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN), and to ultraviolet B (UVB) irradiation. We examined both cell proliferation and MT expression. Cell proliferation was maximally stimulated by 100 microM Zn2+ supply and was markedly inhibited by zinc deprivation or UVB irradiation. Zinc and UVB irradiation both increased MTI and/or MTII as detected by immunocytochemistry and enhanced the baseline level of MT-IIA mRNA, whereas TPEN treatment inhibited MT basal expression. Zinc partially prevented the concentration-dependent, UVB-induced decrease in cell proliferation. On the other hand, TPEN partially prevented the UVB-induced increase in MTIIA mRNA. These results suggest that zinc is involved in defense mechanisms of skin keratinocytes and in their stress-induced response.

Blotting, Northern↗
PubMed1999

Zinc protects against ultraviolet A1-induced DNA damage and apoptosis in cultured human fibroblasts.

Ultraviolet A1 (UVA1) radiation generates reactive oxygen species and the oxidative stress is known as a mediator of DNA damage and of apoptosis. We exposed cultured human cutaneous fibroblasts to UVA1 radiation (wavelengths in the 340-450-nm range with emission peak at 365 nm) and, using the alkaline unwinding method, we showed an immediate significant increase of DNA strand breaks in exposed cells. Apoptosis was determined by detecting cytoplasmic nucleosomes (enzyme-linked immunosorbent assay method) at different time points in fibroblasts exposed to different irradiation doses. In our conditions, UVA1 radiation induced an early (8 h) and a delayed (18 h) apoptosis. Delayed apoptosis increased in a UVA dose-dependent manner. Zinc is an important metal for DNA protection and has been shown to have inhibitory effects on apoptosis. The addition of zinc (6.5 mg/L) as zinc chloride to the culture medium significantly decreased immediate DNA strand breaks in human skin fibroblasts. Moreover, zinc chloride significantly decreased UVA1-induced early and delayed apoptosis. Thus, these data show for the first time in normal cutaneous cultured cells that UVA1 radiation induces apoptosis. This apoptosis is biphasic and appears higher 18 h after the stress. Zinc supplementation can prevent both immediate DNA strand breakage and early and delayed apoptosis, suggesting that this metal could be of interest for skin cell protection against UVA1 irradiation.

Apoptosis↗
PubMed1999

Plasma vitamin A, E, and beta-carotene levels in adult post-partum Algerian women.

Vitamins A and E are essential for foetal growth, reproduction, and lactation. In this article we report the results of a study, lead in three Eastern Algeria cities, that involved 786 post-partum women and 250 control. Plasma levels of vitamins A, E, beta-carotene, and some nutritional indexes were measured in both groups. In control women, plasma retinol and beta-carotene levels were significantly lower in Algeria than in France (retinol: 1.4 +/- 0.42 vs. 1.78 +/- 0.53 mumol/l; beta-carotene: 0.35 +/- 0.261 vs. 0.94 +/- 0.611). These differences could be the consequence of different beta-carotene and retinol intakes. In Algeria, comparisons between post-partum women and controls, showed that plasma vitamin A and beta-carotene levels were significantly lower in post-partum than in control women. This fact, and the lower level of retinol in control women, raises the question of supplementation for pregnant women in Algeria, at least for those with the lowest standard of living whose protein and zinc levels are also very low after delivery. Plasma vitamin E levels and vitamin E/total lipid ratios were not different in Algeria and in France. Vitamin E concentration was higher during pregnancy, but the vitamin E/total lipid ratio was significantly lower, which shows a relative deficiency at the end of pregnancy. Comparisons of plasma vitamin E levels, at delivery, in primiparous and in multiparous women reveal a better tocopherol status in multiparous women. This difference could reflect an adaptive response to oxidative stress in multiparous women.

Adolescent↗