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Biomedical subjects

M Vidal

Publications and source records attributed to M Vidal.

At least 37 records · Page 2Linked to original sources
PubMed2004

1alpha-Hydroxylase transactivation by gamma-interferon in murine macrophages requires enhanced C/EBPbeta expression and activation.

gamma-Interferon [gamma-IFN] induction of macrophage 1alpha-hydroxylase mRNA and activity causes severe hypercalcemia in granulomatous disorders. These studies demonstrate transcriptional regulation. gamma-IFN induces the activity of the murine 1alpha-hydroxylase [-1651; +22] promoter in the murine macrophage cell line Raw 264.7 only after a 24h exposure. This slow kinetics is incompatible with classical gamma-IFN-mediated transactivation. In fact, gamma-IFN response mapped to the minimal [-85; +11] promoter, which lacks GAS or ISRE sites but contains a putative C/EBPbeta site. C/EBPbeta is a gamma-IFN inducible gene and a novel mediator of gamma-IFN-regulated transcription. As expected for a C/EBPbeta-driven transcription, ectopic C/EBPbeta expression was sufficient to increase 1alpha-hydroxylase activity, enhance minimal promoter activity and potentiate the induction of this promoter by gamma-IFN. Importantly, the dominant negative C/EBPbeta isoform antagonized C/EBPbeta-transcriptional activity. gamma-IFN induction of C/EBPbeta expression is not sufficient for gamma-IFN induction of minimal promoter activity. There is also a cell-specific induction of C/EBPbeta-transcriptional activity by gamma-IFN. In Raw cells, specific inhibition of gamma-IFN induction of endogenous-C/EBPbeta phosphorylation by MEKK1 markedly reduced basal promoter activity and the response to gamma-IFN. We conclude that gamma-IFN-induction of C/EBPbeta expression and activation by phosphorylation contributes to gamma-IFN-transcriptional control of 1alpha-hydroxylase expression in murine macrophages.

Animals↗
PubMed2004

The effects of smoking and its cessation on 8-epi-PGF2alpha and transforming growth factor-beta 1 in Type 1 diabetes mellitus.

BACKGROUND: Oxidative stress and transforming growth factor-beta 1 (TGF-beta1) are associated with diabetic complications, and smoking is a risk factor. AIMS: This study aimed (i) to compare urinary 8-epi-PGF2alpha and plasma and urinary TGF-beta1 levels obtained in heavy smokers with Type 1 diabetes with those observed in age-matched non-smoker patients with Type 1 diabetes and controls, and (ii) to investigate the effects of smoking cessation (SC) on the above-mentioned parameters in patients with Type 1 diabetes. METHODS AND RESULTS: Compared with control subjects (n = 12), non-smoker diabetic patients (n = 12) presented higher values of urinary 8-epi-PGF2alpha (74.2 +/- 29.6 vs. 29.6 +/- 11.1 pg/mg urinary creatinine, P = 0.01), plasma TGF-beta1 (7.7 +/- 4.7 vs. 3.6 +/- 1.7 ng/ml, P = 0.001) and urinary TGF-beta1 (15.3 +/- 6.3 vs. 8.1 +/- 4.4 ng/mg urinary creatinine, P = 0.02). Compared with non-smoker diabetic patients, smoker diabetic patients (n = 16) showed higher levels of urinary 8-epi-PGF2alpha (107.8 +/- 40.2 vs. 74.2 +/- 29.6 pg/mg urinary creatinine, P = 0.0001), plasma TGF-beta1 (12.6 +/- 4.9 vs. 7.7 +/- 4.7 ng/ml, P = 0.001) and urinary TGF-beta1 (27.5 +/- 16.0 vs. 15.3 +/- 6.3 ng/mg urinary creatinine, P = 0.01). Smoker patients were included in a smoking cessation programme. In the 10 patients that gave up smoking there was a reduction of urinary 8-epi-PGF2alpha (basal: 110.47 +/- 47.0 vs. week 12: 73.2 +/- 25.6; P < 0.001), plasma TGF-beta1 (basal: 11.2 +/- 5.9 vs. week 12: 4.89 +/- 2.25; P < 0.01) and urinary TGF-beta1 (basal: 18.12 +/- 9.27 vs. week 12: 10.32 +/- 2.0; P < 0.01) levels. CONCLUSIONS: In patients with Type 1 diabetes, smoking increased oxidative stress, evaluated by lipid peroxidation, and TGF-beta1 production. Smoking cessation decreased these parameters, providing additional support to encourage diabetic patients to give up smoking.

Adult↗
PubMed2003

[Malaise with sweating induced by eye-drop. A case of iatrogenic pathology caused by diagnostic error].

INTRODUCTION: Eye-drops can provoke various systemic side effects and diagnosis of an iatrogenic pathology can made difficult. Observation For 4 months, and 80 year-old man had experienced severe recurrent episodes of sweating concomitant with shaking of the legs. Alpha stimulating eye-drops, prescribed for his glaucoma, were at the origin of these problems. On withdrawal of the latter, the symptoms regressed. DISCUSSION: Diagnosis of an iatrogenic pathology was made after 3 months of medical explorations. The delay in diagnosis was prolonged because the patient had not mentioned the use of an active ingredient, since it was in the form of eye-drops. CONCLUSION: The search for drug-induced causes must be systematic when faced with any unexplained symptom and must include all the active ingredients, whatever their form of administration.

Aged↗
PubMed2002

An overview of the effect of organic matter on soil-radiocaesium interaction: implications in root uptake.

This paper aims to give an overview of the effect of organic matter on soil-radiocaesium interaction and its implications on soil-to-plant transfer. Studies carried out after the Chernobyl accident have shown that high 137CS soil-to-plant transfer persists in organic soils over years. In most of these soils, the specific sites in clays control radiocaesium adsorption, organic compounds having an indirect effect. Only in organic soils with more than 95% of organic matter content and negligible clay content does adsorption occur mostly on non-specific sites. After a contamination event, two main factors account for the high transfer: the low solid-liquid distribution coefficient, which is due to the low clay content and high NH4+ concentration in the soil solution, and the low K+ availability, which enhances root uptake. The estimation of the reversibly adsorbed fraction, by means of desorption protocols, agrees with the former conclusions, since it cannot be correlated with the organic matter content and shows the lack of specificity of the adsorption in the organic phase. Moreover, the time-dependent pattern of the exchangeable fraction is related to soil-plant transfer dynamics.

Adsorption↗
PubMed2001

Human T cell leukemia virus type 1 Tax associates with a molecular chaperone complex containing hTid-1 and Hsp70.

Tax, an oncogenic viral protein encoded by human T cell leukemia virus type 1 (HTLV-1), induces cellular transformation of T lymphocytes by modulating a variety of cellular gene expressions [1]. Identifying cellular partners that interact with Tax constitutes the first step toward elucidating the molecular basis of Tax-induced transformation. Here, we report a novel Tax-interacting protein, hTid-1. hTid-1, a human homolog of the Drosophila tumor suppressor protein Tid56, was initially characterized based on its interaction with the HPV-16 E7 oncoprotein [2]. hTid-1 and Tid56 are members of the DnaJ family [2,3], which contains a highly conserved signature J domain that regulates the activities of heat shock protein 70 (Hsp70) by serving as cochaperone [4-6]. In this context, the molecular chaperone complex is involved in cellular signaling pathways linked to apoptosis, protein folding, and membrane translocation and in modulation of the activities of tumor suppressor proteins, including retinoblastoma, p53, and WT1[7-12]. We find that expression of hTid-1 inhibits the transformation phenotype of two human lung adenocarcinoma cell lines. We show that Tax interacts with hTid-1 via a central cysteine-rich domain of hTid-1 while a signature J domain of hTid-1 mediates its binding to Hsp70 in HEK cells. Importantly, Tax associates with the molecular chaperone complex containing both hTid-1 and Hsp70 and alters the cellular localization of hTid-1 and Hsp70. In the absence of Tax, expression of the hTid-1/Hsp70 molecular complex is targeted to perinuclear mitochondrial clusters. In the presence of Tax, hTid-1 and its associated Hsp70 are sequestered within a cytoplasmic "hot spot" structure, a subcellular distribution that is characteristic of Tax in HEK cells.

Binding Sites↗
PubMed2001

Effect of crown ethers on structure, stability, activity, and enantioselectivity of subtilisin Carlsberg in organic solvents.

Colyophilization or codrying of subtilisin Carlsberg with the crown ethers 18-crown-6, 15-crown-5, and 12-crown-4 substantially improved enzyme activity in THF, acetonitrile, and 1,4-dioxane in the transesterification reactions of N-acetyl-L-phenylalanine ethylester and 1-propanol and that of (+/-)-1-phenylethanol and vinylbutyrate. The acceleration of the initial rate, V(0), ranged from less than 10-fold to more than 100-fold. All crown ethers activated subtilisin substantially, which excludes a specific macrocyclic effect from being responsible. The secondary structure of subtilisin was studied by Fourier-transform infrared (FTIR) spectroscopy. 18-Crown-6 and 15-crown-5 led to a more nativelike structure of subtilisin in the organic solvents employed when compared with that of the dehydrated enzyme obtained from buffer alone. However, the high level of activation with 12-crown-4 where this effect was not observed excluded overall structural preservation from being the primary cause of the observed enzyme activation. The conformational mobility of subtilisin was investigated by performing thermal denaturation experiments in 1,4-dioxane. Although only a small effect of temperature on subtilisin structure was observed for the samples prepared with or without 12-crown-4, both 18-crown-6 and 15-crown-5 caused the enzyme to denature at quite low temperatures (38 degrees C and 56 degrees C, respectively). No relationship between this property and V(0) was evident, but increased conformational mobility of the protein decreased its storage stability. The possibility of a "molecular imprinting" effect was also tested by removing 18-crown-6 from the subtilisin-18-crown-6 colyophilizate by washing. V(0) was only halved as a result of this procedure, an effect insignificant compared with the ca. 80-fold rate enhancement observed prior to washing in THF. This suggests that molecular imprinting is likely the primary cause of subtilisin activation by crown ethers, as recently suggested.

Acetonitriles↗
PubMed2001

Evidence that HAX-1 is an interleukin-1 alpha N-terminal binding protein.

During studies aimed at understanding the function of the N-terminal peptide of interleukin-1 alpha (IL-1 NTP, amino acids 1-112), which is liberated from the remainder of IL-1 alpha during intracellular processing, we identified by yeast two-hybrid analysis a putative interacting protein previously designated as HAX-1. In vitro binding studies and transient transfection experiments confirmed that HAX-1 can associate with the IL-1 NTP. HAX-1 was first identified as a protein that associates with HS1, a target of non-receptor protein tyrosine kinases within haematopoietic cells. Recent data have also revealed interactions between HAX-1 and three disparate proteins, polycystin-2 (derived from the PKD2 gene), a protein linked to polycystic kidney disease, cortactin, and Epstein-Barr virus nuclear antigen leader protein (EBNA-LP). Sequence analysis of different HAX-1 binding domains revealed a putative consensus binding motif that is present in various intracellular proteins. Overlapping peptides comprising the IL-1 NTP were synthesized, and binding experiments revealed that discrete peptides were capable of interacting with HAX-1. HAX-1 may serve to retain the IL-1 NTP in the cytoplasm, and complex formation between the IL-1 NTP and HAX-1 may play a role in motility and/or adhesion of cells.

Adaptor Proteins, Signal Transducing↗
PubMed2001

HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway.

It has been previously shown that the HIV-1 envelope glycoprotein 120 (gp120) activates cell signaling by CXCR4, independently of CD4. The present study examines the involvement of different intracellular signaling pathways and their physiopathologic consequences following the CD4-independent interaction between CXCR4 or CCR5 and gp120 in different cell types: primary T cells, CD4(-)/CXCR4(+)/CCR5(+) T cells, or glioma cells. These interactions were compared with those obtained with natural ligands, stromal cell-derived factor 1 alpha (SDF-1alpha) (CXCL12) and macrophage inflammatory protein 1 beta (MIP-1beta) (CCL4) of their respective coreceptors. Thus, both p38 and SAPK/Jun N-terminal kinase mitogen-activated protein kinases (MAPKs) are activated on stimulation of these cells with either T- or M-tropic gp120, as well as with SDF-1alpha or MIP-1beta. In contrast, extracellular signal-related kinase 1 and 2 MAPKs are only activated by MIP-1beta but not by M-tropic gp120. Importantly, T- and M-tropic gp120 are able to induce the secretion of matrix metalloproteinase 9 (MMP-9), an extracellular metalloproteinase present in cerebrospinal fluid of patients with HIV-1 by T cells or glioma cells. Specific inhibition of MAPK p38 activation resulted in a complete abrogation of the induction of the MMP-9 pathogenic factor expression by gp120 or chemokines in both cell types. Because neurodegenerative features in acquired immune deficiency syndrome dementia may involve demyelinization by MMP-9, the specific targeting of p38 could provide a novel means to control HIV-induced cytopathogenic effects and cell homing to viral replication sites. (Blood. 2001;98:541-547)

Animals↗
PubMed2001

Histone deacetylase-dependent transcriptional repression by pRB in yeast occurs independently of interaction through the LXCXE binding cleft.

We have developed a yeast model system to address transcriptional repression by the retinoblastoma protein (pRB). When fused to the DNA-binding domain of Gal4p (DB-pRB), pRB can repress transcription of reporter genes containing Gal4p binding sites; the histone deacetylase activity encoded by yeast RPD3 is required for DB-pRB repression. Mutation of the LXCXE binding cleft in pRB, a region reported to be required for histone deacetylase recruitment, does not interfere with pRB-mediated repression. From these findings based on yeast experiments, we surmise that the small pocket region of pRB must contain an additional domain that confers histone deacetylase-dependent transcriptional repression. This hypothesis was verified by experiments examining pRB-dependent histone deacetylase association in mammalian cells. In addition to RPD3, repression by pRB in yeast requires MSI1, an ortholog of RbAp48, but not SIN3 or SAP30. By comparing the genetic requirements of DB-pRB repression in yeast to those of other DB-repressor fusions, we can suggest a mechanism by which pRB recruits histone deacetylase activity.

Binding Sites↗
PubMed2001

A soil sampling strategy for mapping trace element concentrations in a test area.

A sampling strategy, based on previous knowledge of a test area, was compared with a Reference Sampling in the frame of the EU-funded CEEM project. The aim was a comparison of sampling strategies for the drafting of concentration maps for a set of trace elements (Cd, Pb, Cu and Zn), with three-dimension information that can be used for risk assessment. The main constraint was that only 15 soil samples were to be analysed. The test area (in Dornach, Switzerland) included different soil types and land uses (forest, arable land and permanent grasslands). The sampling strategy proposed defined strata on the basis of land use, then applying a systematic regular sampling within each stratum. A composite sample was formed from each individual sample. In forests, H and Ah horizons were taken separately. In arable lands, a depth within the ploughed layer (0-15 cm) was analysed. In grasslands, samples were taken at two depths (0-10 and 10-20 cm) to provide information on the vertical variability. The comparison of the results obtained with those derived from the Reference Sampling allowed us to estimate if the information obtained from the proposed sampling strategy was sufficiently representative for an assessment of the level of elements considered. It was concluded that recommendations on sampling strategy depend on the interaction pattern of the element. In this case, for mobile trace elements, such as Cd, the information derived from sampling of two soil layers was not as important as that for the rest of metals studied that accumulated in the upper layer. If the H horizons in forests was not considered this led to unreliable predictions of the concentration levels, since the concentrations in H and Ah horizons differed irrespective of whether they were expressed in mg kg(-1) (the H horizon was enriched in those trace elements, except for Cd) and in mg m(-2) (the low bulk density of the H horizon led to a lower trace element level than in Ah horizon). Finally, in undisturbed systems such as grasslands, sampling 0-10 cm instead of 0-20 cm is recommended to prevent dilution of the concentration of trace elements.

Agriculture↗
PubMed2001

High-throughput yeast two-hybrid assays for large-scale protein interaction mapping.

Protein-protein interactions play fundamental roles in many biological processes. Hence, protein interaction mapping is becoming a well-established functional genomics approach to generate functional annotations for predicted proteins that so far have remained uncharacterized. The yeast two-hybrid system is currently one of the most standardized protein interaction mapping techniques. Here, we describe the protocols for a semiautomated, high-throughput, Gal4-based yeast two-hybrid system.

Culture Media↗
PubMed2001

Selection of Mycobacterium sp. strains with capacity to biotransform high concentrations of beta-sitosterol.

In this work, phytosterol-biotransforming strains were selected from Mycobacterium sp., using a high concentration of beta-sitosterol. The selection was made by culturing the strains in a medium enriched with 14 g beta-sitosterol/l as the unique source of carbon. During 2 months, the bacterial cultures were transferred successively. The extraction of the biotransformation products was made with methanol and ethyl acetate. The qualitative and quantitative analysis was made by means of thin-layer chromatography, gas-liquid chromatography (GLC) and GLC-mass spectrometry. Under these conditions, it was observed that after seven transfers, the strains MYcobacterium sp. MB-3683 and the Mycobacterium fortuitum B-11045 increased their biotransformation capacity from 20% to 64% and from 34% to 55%, respectively. The products in the highest proportion identified for each trial were androstenedione and androstadienedione. The results suggest that the high substrate concentration could be a selective mechanism to obtain strains more efficient in the biotransformation of beta-sitosterol into steroidal bases.

Androstadienes↗
PubMed2001

Soil- and plant-based countermeasures to reduce 137Cs and 90Sr uptake by grasses in natural meadows: the REDUP project.

The effectiveness of a set of soil- and plant-based countermeasures to reduce 137Cs and 90Sr transfer to plants was tested in natural meadows in the area affected by Chernobyl fallout. Countermeasures comprised the use of agricultural practices (disking + ploughing, liming and NPK fertilisation), addition of soil amendments and reseeding with a selection of grass species. Disking + ploughing was the most effective treatment, whereas the K fertiliser doses applied were insufficient to produce a significant increase in K concentration in soil solution. The application of some agricultural practices was economically justifiable for scenarios with a high initial transfer, such as 137Cs-contaminated organic soils. The use of soil amendments did not lead to a further decrease in transfer. Laboratory experiments demonstrated that this was because of their low radionuclide sorption properties. Finally, experiments examining the effect of plant species on radionuclide transfer showed that both transfer and biomass can depend on the plant species, indicating that those with high radionuclide root uptake should be avoided when reseeding after ploughing.

Agriculture↗
PubMed2001

Active, passive and snapshot exploration in a virtual environment: influence on scene memory, reorientation and path memory.

We investigated the importance of active, passive and snapshot exploration on spatial memory in a virtual city. The exploration consisted in traveling along a series of streets. 'Active exploration' was performed by giving directions to the subject who controlled his displacement with a joystick. During 'passive' exploration, the travel was imposed by the computer. Finally, during 'snapshot exploration', simple views of the scene were presented sequentially every 4 m. Travel velocity was the same in all cases. The three visual exploration modes were compared with three spatial memory measures: (1) scene recognition, (2) at the end of the path, reorientation toward the departure point and (3) drawings of the path shape. Scene recognition and estimation of the direction of the starting point of the path were not affected by the mode of exploration. In contrast, reproduction of the shape of the path was affected: the errors of reproduction were greater for the snapshot exploration than for the other two conditions; there was no difference between the other two conditions. These results suggest that (1) 2D image features from a visual scene are memorized. Moreover, (2) pointing towards the origin of the path relies on motion duration integration or a frame of reference integrated during displacement. Finally, (3) drawing the path shape involves a deliberate reconstruction process.

Adult↗
PubMed2001

SH2 and SH3 domains as targets for anti-proliferative agents.

The Src homology domains SH2 and SH3 are small modular protein motifs about 100 and 60 amino acids long, respectively. SH2 domains interact with phosphotyrosine residues, whereas SH3 domains recognize proline-rich motifs of their interacting partners. SH2 and SH3 domains are frequently found in signaling proteins such as small adaptors and in enzymes such as kinases, lipases and phosphatases, in which they differ from the catalytic motif and constitute recognition modules. SH2 and SH3 domains are also found in oncoproteins and in proteins overexpressed in deregulated signaling pathways in tumor cells. The highly folded structures of these domains have been characterized alone and complexed with the essential fragments of their targets. Therefore, based on molecular data, inhibitors of interactions with SH2 and SH3 domains are considered to be potential antitumor agents. Current results are very promising, as inhibitors with very efficient anti-proliferative activity in tumor cells have been reported. This paper describes SH2 and/or SH3 domain-containing proteins that may constitute targets for anticancer therapeutics. It also deals with the essential structural data concerning SH2 and SH3 domains, and the rational design of inhibitors. Some of the more recent pharmacological results obtained with these compounds are also discussed.

Amino Acid Sequence↗