PubMed Health⌕ Search

Biomedical subjects

M Faure

Publications and source records attributed to M Faure.

At least 37 records · Page 2Linked to original sources
PubMed2001

Inhibition of natural killer cell activation signals by killer cell immunoglobulin-like receptors (CD158).

The killer cell immunoglobulin-like receptor (KIR) family includes receptors that bind to HLA class I molecules on target cells and inhibit natural killer (NK)-cell cytotoxicity, and receptors such as KIR3DL7 with no known ligand and function. Inhibitory KIR recruit the tyrosine phosphatase SHP-1 to block signals transduced by any one of a number of activation receptors. Inhibition of overall protein tyrosine phosphorylation by SHP-1 during binding of KIR to MHC class I on target cells is selective, suggesting that a limited number of substrates are dephosphorylated by SHP-1. We have chosen to study KIR inhibition as it occurs during binding of KIR to MHC class I on target cells, despite the technical limitations inherent to studies of processes regulated by cell contact. KIR binding to MHC class I on target cells inhibits tyrosine phosphorylation of the activation receptor 2B4 (CD244) and disrupts adhesion of NK cells to target cells. Inhibition of proximal events in NK activation may increase the availability of NK cells by liberating them from non-productive interactions with resistant target cells. As the receptors and the signaling pathways that induce NK cytotoxicity are not fully characterized, elucidation of the inhibitory mechanism employed by KIR may provide insight into NK activation.

Amino Acid Sequence↗
PubMed2001

Branched-chain amino acid aminotransferase activity decreases during development in skeletal muscles of sheep.

The catabolism of branched-chain amino acid (BCAA) differs between sheep and monogastric animals. The transamination of BCAA seems to be affected by development of the sheep. We studied the developmental changes in the activity and expression of the BCAA aminotransferase (BCAT) isoenzymes in skeletal muscle of sheep. Five muscles were taken from fetus, newborn, preruminant and ruminant lambs. BCAT specific activity and the contribution of each BCAT isoenzyme [mitochondrial and cytosolic (BCATm and BCATc, respectively)] were quantified using radioenzymatic and immunoprecipitation assays. BCATm and BCATc mRNAs were assessed by real-time reverse transcription-polymerase chain reaction. BCAT specific activities were 62% (diaphragma) to 83% (longissimus dorsi) lower in the ruminant lamb than in the fetal sheep. BCATm and BCATc were both expressed in sheep skeletal muscle at all developmental stages. BCATc was mainly responsible for the developmental decrease in BCAT specific activity. BCATc specific activities were 77% (diaphragma) to 92% (longissimus dorsi) lower in the ruminant lamb than in the fetal sheep, whereas BCATm specific activities were only 36% (semimembranosus) to 56% (longissimus dorsi) lower. BCATc and BCATm mRNAs in the longissimus dorsi were not affected by development of the sheep. The developmental decrease in BCATc activity, and to a lesser extent in BCATm activity, probably involves posttranscriptional mechanisms in sheep. The present results are consistent with lower in vivo metabolism of BCAA in ruminant than in the fetal sheep.

Animals↗
PubMed2001

[Cutaneous adverse drug reactions: enhanced imputation score by skin testing].

INTRODUCTION: A careful diagnosis and the identification of the causative drug after a cutaneous adverse reaction can avoid relapses. Skin tests facilitate the identification of the causative molecule by producing a hypersensitivity reaction at the application site. Adverse drug reactions are reported to Pharmacovigilance Centres who determine the imputation score of the suspected drugs. The aim of this study was to assess to what extent skin testing after a suspected allergic drug reaction can be helpful to identify the causative drug and whether an impact on the final imputation score could be evidenced. METHOD: A 18-month prospective study was performed. All patients with a history of cutaneous adverse drug reaction of suspected immunoallergic origin were included provided skin tests could be performed within 6 to 12 weeks after the adverse drug reaction. The imputation score was determined using the French imputation method prior to and after skin testing. RESULTS: Thirthy-nine patients were included in the study. Positive skin tests were observed in 11 of 20 patients with a C2S2 (I2: plausible) initial imputation score and in 6 of 15 patients with a C2S1 (I1: doubtful) initial imputation score. One patient with a C1S1 (I1: doubtful) initial imputation score had positive skin tests. DISCUSSION: The results of skin tests helped change the imputation score of the suspected drug in 18 patients out of 39. In 55 p. 100 of cases, the imputation score was increased from C2S2 (I2) to C2S3 (I3: likely) and from C2S1 (I1) to C2S3 (I3) in 40 p. 100 of cases. The increase in imputation scores was helpful to improve warning signals after an immunoallergic reaction. Skin tests led to a more accurate diagnosis in 50 p. 100 of cases. Thus, more adequate advices for further drug treatment were possible, particularly in avoiding the irrelevant prohibition of innocent drugs.

Adolescent↗
PubMed2001

[Familial hyperchylomicronemia with a new mutation of the lipoprotein lipase gene].

INTRODUCTION: Familial hyperchylomicronemia is a rare autosomal recessive disease caused by lipoprotein lipase deficiency. CASE-REPORT: A nine month-old girl presented with eruptive xanthomas revealing a familial hyperchylomicronemia. No lipoprotein lipase activity was found. DNA analysis revealed a novel homozygous non-sense mutation of the lipoprotein lipase gene at the codon 288. The parents were heterozygous carriers. DISCUSSION: Familial hyperchylomicronemia usually presents with eruptiva xanthomas, abdominal pain, pancreatic manifestation and lipemia retinalis. Papulo-nodular xanthomas occur more frequently in children as in our case. Eighty lipoprotein lipase gene mutations have been recorded to date. The gene locates on chromosome 8. Only 9 non-sense mutations have been described which lead to a truncated protein. In our case, no enzymatic activity was detected probably due to an absence of secretion of the enzyme, even though catalytic activity persisted. The homozygous carrier status leads to hyperchylomicronemia whereas the heterozygote status may lead to mixed hyperlipidemia with an increased risk of atherosclerosis. The screening of lipoprotein lipase gene mutations should be carried out in all families with hyperchylomicronemia, regardless of the presence or absence of xanthomas.

Chromosome Aberrations↗
PubMed2000

Sheep cytosolic branched-chain amino acid aminotransferase: cDNA cloning, primary structure and molecular modelling and its unique expression in muscles.

This paper presents the cloning and the molecular modelling of the cytosolic branched-chain amino acid aminotransferase (BCATc) from sheep brain. The sheep BCATc cDNA (3 kb) encodes a mature polypeptide of 385 amino acids with a calculated molecular mass of 43072.93 Da. The sequence of the sheep BCATc cDNA is more similar to other mammalian BCATc cDNAs (53-87% identical) than to the sheep mitochondrial branched-chain amino acid aminotransferase (52%). Sheep BCATc belongs to the IV Folding class of pyridoxal-5'-phosphate-depending enzymes. Based on the known structure of the branched-chain amino acid aminotransferase (BCAT) from Escherichia coli, a molecular model of sheep BCATc (amino acid residues 62-385) was built. This is the first three-dimensional model of any mammalian BCAT. It suggests that the enzymatic mechanism of sheep BCATc and likely of all mammalian BCAT is very similar to the mechanism of the E. coli BCAT and confirms the hypotheses regarding to the substrate binding sites of E. coli BCAT. Sheep skeletal muscle, which is the main in vivo site for transamination of branched-chain amino acids, exhibits an unique expression of BCATc.

Amino Acid Sequence↗
PubMed2000

[Perianal streptococcal dermatitis].

BACKGROUND: Pediatric perianal streptococcal dermatitis (PSD) is a well-defined clinical entity. However, its highly uniform presentation remains surprisingly unrecognized by many practitioners 33 years after its first description. CASE REPORT: A seven-year-old girl had a three-week history of perianal and vulva redness with well-defined margins. Functional symptoms associated perirectal tenderness and pain during defecation, which was responsible for constipation. At onset she also presented with a sore throat, which resolved spontaneously, and she had been complaining for a few days about a perioral impetigo. She received mycostatin unsuccessfully for an alleged candidiasis. Positive cultures for group A beta-hemolytic streptococci from both perirectal and perioral swabs confirmed the diagnosis of PSD. Therapy with amoxicillin (50 mg/kg/d) was prescribed for ten days. Perianal lesions were cleared by day 2. CONCLUSION: Since PSD can masquerade as candidiasis, psoriasis, seborrheic dermatitis, inflammatory bowel disease or even sexual abuse, it remains an underdiagnosed entity. This situation leads to delayed diagnosis and treatment which in turn might increase the frequency of secondary complications related to streptococcal infections (i.e., post-streptococcal acute nephritis and rheumatism, guttate psoriasis, etc.).

Amoxicillin↗
PubMed2000

Multiple eruptive dermatofibromas in a patient with HIV infection: case report and literature review.

Multiple eruptive dermatofibromas have been reported in the setting of autoimmune diseases treated with immunosuppressive drugs and more recently in the course of human immunodeficiency virus (HIV) infection. We report herein the ninth case of multiple eruptive dermato fibromas associated with HIV infection. The relevant literature is reviewed and the differences of these lesions from "ordinary" dermatofibromas are discussed.

HIV Infections↗
PubMed2000

Interaction between the lipoamide-containing H-protein and the lipoamide dehydrogenase (L-protein) of the glycine decarboxylase multienzyme system 2. Crystal structures of H- and L-proteins.

The glycine decarboxylase complex consists of four different component enzymes (P-, H-, T- and L-proteins). The 14-kDa lipoamide-containing H-protein plays a pivotal role in the complete sequence of reactions as its prosthetic group (lipoic acid) interacts successively with the three other components of the complex and undergoes a cycle of reductive methylamination, methylamine transfer and electron transfer. With the aim to understand the interaction between the H-protein and its different partners, we have previously determined the crystal structure of the oxidized and methylaminated forms of the H-protein. In the present study, we have crystallized the H-protein in its reduced state and the L-protein (lipoamide dehydrogenase or dihydrolipoamide dehydrogenase). The L-protein has been overexpressed in Escherichia coli and refolded from inclusion bodies in an active form. Crystals were obtained from the refolded L-protein and the structure has been determined by X-ray crystallography. This first crystal structure of a plant dihydrolipoamide dehydrogenase is similar to other known dihydrolipoamide dehydrogenase structures. The crystal structure of the H-protein in its reduced form has been determined and compared to the structure of the other forms of the protein. It is isomorphous to the structure of the oxidized form. In contrast with methylaminated H-protein where the loaded lipoamide arm was locked into a cavity of the protein, the reduced lipoamide arm appeared freely exposed to the solvent. Such a freedom is required to allow its targeting inside the hollow active site of L-protein. Our results strongly suggest that a direct interaction between the H- and L-proteins is not necessary for the reoxidation of the reduced lipoamide arm bound to the H-protein. This hypothesis is supported by biochemical data [Neuburger, M., Polidori, A.M., Piètre, E., Faure, M., Jourdain, A., Bourguignon, J., Pucci, B. & Douce, R. (2000) Eur. J. Biochem. 267, 2882-2889] and by small angle X-ray scattering experiments reported herein.

Amino Acid Oxidoreductases↗
PubMed2000

Interaction between the lipoamide-containing H-protein and the lipoamide dehydrogenase (L-protein) of the glycine decarboxylase multienzyme system. 1. Biochemical studies.

Lipoamide dehydrogenase or dihydrolipoamide dehydrogenase (EC 1.8.1. 4) is the E3-protein component of the mitochondrial 2-oxoacid dehydrogenase multienzyme complexes. It is also the L-protein component of the glycine decarboxylase system. Although the enzymology of this enzyme has been studied exhaustively using free lipoamide as substrate, no data are available concerning the kinetic parameters of this enzyme with its physiological substrates, the dihydrolipoyl domain of the E2 component (dihydrolipoyl acyltransferase) of the 2-oxoacid dehydrogenase multienzyme complexes or the dihydrolipoyl H-protein of the mitochondrial glycine decarboxylase. In this paper, we demonstrate that Tris(2-carboxyethyl)phosphine, a specific disulfide reducing agent, allows a continuous reduction of the lipoyl group associated with the H-protein during the course of the reaction catalysed by the L-protein. This provided a valuable new tool with which to study the catalytic properties of the lipoamide dehydrogenase. The L-protein displayed a much higher affinity for the dihydrolipoyl H-protein than for free dihydrolipoamide. The oxidation of the dihydrolipoyl H-protein was not affected by the presence of structurally related analogues (apoH-protein or octanoylated H-protein). In marked contrast, these analogues strongly and competitively inhibited the decarboxylation of the glycine molecule catalysed by the P-protein component of the glycine decarboxylase system. Small unfolded proteolytic fragments of the H-protein, containing the lipoamide moiety, displayed Km values for the L-protein close to that found for the H-protein. On the other hand, these fragments were not able to promote the decarboxylation of the glycine in the presence of the P-protein. New highly hydrophilic lipoate analogues were synthesized. All of them showed Km and kcat/Km values very close to that found for the H-protein. From our results we concluded that no structural interaction is required for the L-protein to catalyse the oxidation of the dihydrolipoyl H-protein. We discuss the possibility that one function of the H-protein is to maintain a high concentration of the hydrophobic lipoate molecules in a nonmicellar state which would be accessible to the catalytic site of the lipoamide dehydrogenase.

Amino Acid Oxidoreductases↗