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Biomedical subjects

M Giraud

Publications and source records attributed to M Giraud.

At least 19 recordsLinked to original sources
PubMed2004

Association of the gene encoding the delta-subunit of the muscle acetylcholine receptor (CHRND) with acquired autoimmune myasthenia gravis.

The muscle acetylcholine receptor (AChR) is the main target self-antigen in acquired autoimmune myasthenia gravis (MG). Here, we investigated an association of MG with the CHRND gene encoding the delta-subunit of the AChR. Using a microsatellite repeat located in the second intron of the gene, we observed a preferential transmission of the allele 268 in 114 one-generation families with one myasthenic child (Pc=0.0154). This allele was also over-represented in a group of 350 unrelated nonthymoma MG patients (OR=1.78, P=0.038), but not in 84 thymoma patients, compared to 168 healthy controls. Moreover, among nonthymoma patients, those lacking serum anti-titin antibodies appeared to be best associated (OR=2.07, P=0.017). In contrast, there was no distortion in the transmission of a single-nucleotide substitution polymorphisms (SNPs) in the 3' untranslated region of CHRND nor in that of two SNPs located in the closely linked CHRNG gene, 4.5 kb telomeric to CHRND. The data warrant a detailed investigation of CHRND polymorphism in MG patients.

Child, Preschool↗
PubMed2001

Linkage of HLA to myasthenia gravis and genetic heterogeneity depending on anti-titin antibodies.

BACKGROUND: MG is an autoimmune disease of the neuromuscular junction. MG with thymus hyperplasia has been associated with, but not genetically linked to, the HLA-DR3 haplotype. OBJECTIVE: To re-evaluate the association of HLA with MG in 656 patients with generalized disease and to test linkage of HLA to MG with thymus hyperplasia. METHOD: Patients were genotyped for HLA-DRB1. Data analysis included case-control comparisons after subgrouping patients by thymus histopathology. The transmission of parental alleles to MG offspring with thymus hyperplasia was studied in simplex families using the transmission/disequilibrium test (TDT) as a test of linkage. RESULTS: MG with thymus hyperplasia was positively associated with DR3 (OR = 4.5, p = 1 x 10(-6)) and negatively associated with DR7 (OR = 0.28, p = 1 x 10(-6)), based on both case-control comparisons and TDT. No association was detected with thymomas. Conversely, patients who lacked thymus anomalies but expressed anti-titin antibodies (ATA) had an increase of DR7 (OR = 2.08, p = 4 x 10(-3)) and a decrease of DR3 (OR = 0.33, p = 9 x 10(-3)). CONCLUSIONS: The authors established linkage of HLA to MG and thymus hyperplasia, defining the MYAS1 locus. Moreover, DR3 and DR7, or closely linked genes, have opposing effects on MG phenotypes. Nonthymomatous patients with ATA may be a pathogenetically distinct subset of MG patients.

Adult↗
PubMed2001

Soluble proteins of the nacre of the giant oyster Pinctada maxima and of the abalone Haliotis tuberculata: extraction and partial analysis of nacre proteins.

Several proteins from nacre of the oyster Pinctada maxima and the abalone Haliotis tuberculata were extracted and partly characterized. Proteins dispersed in aragonite were solubilized during demineralization with acetic acid whereas proteins adsorbed on conchiolin were extracted with sodium dodecyl sulfate and beta-mercaptoethanol. The matrix of Pinctada maxima nacre is composed of one main protein with an apparent molecular weight of 20 kDa (p20). This protein was found in the acetic acid soluble fraction of nacre, as well as in the Laemmli-solubilized extract of conchiolin. In addition, the p20 solubilized with acetic acid can form oligomers made of 6 monomers linked together by disulfide bridges. The first N-terminal 21 amino acids of p20 were determined and no homology with known proteins was found. In Haliotis tuberculata nacre, 5 main proteins were solubilized during demineralization and 3 glycoproteins were detected. Stains-all and Alcian blue staining revealed polyanionic proteins in the extracts isolated from Pinctada maxima and Haliotis tuberculata nacre.

Amino Acid Sequence↗
PubMed1999

A side-reaction in the SPPS of Trp-containing peptides.

Syntheses of several Trp-containing peptides on a Wang solid support afforded significant amounts of a side-product. 1H-NMR and MS data showed that an unexpected alkylation by the linker has occurred on the indole nucleus. This was observed whatever the scavenger used, and whatever the position of the Trp residue in the sequence, unless it was in the C-terminal position.

Amino Acid Sequence↗
PubMed1998

Pharmacokinetics of intravenous methylprednisolone and oral prednisone in paediatric patients with inflammatory bowel disease during the acute phase and in remission.

OBJECTIVE: The present study was undertaken to evaluate the influence of inflammatory bowel disease on the pharmacokinetics of intravenous methylprednisolone and prednisolone (after oral administration of prednisone). PATIENTS: Twelve children with inflammatory bowel disease, aged 12.3 years were studied during the active phase and in remission. In 6 patients the disease responded to oral prednisone while 6 did not respond. METHODS: During the acute phase, intravenous methylprednisolone (2 mg x kg(-1)) and oral prednisone (2 mg x kg(-1)) were administered in a random order and blood was sampled over 48 h. Prednisone (2 mg x kg(-1)) was readministered after remission. The concentrations of methylprednisolone and prednisolone were measured by high-pressure liquid chromatography. RESULTS: During the acute phase, the systemic clearance of methylprednisolone was 0.98 (1 kg(-1) x h(-1)) and the elimination half-life was 1.67 h. The area under the plasma concentration-versus-time curve of prednisolone was 4.00 and 3.20 x mg x h x l(-1) respectively during the active disease and remission, while its elimination half-life was 3.51 h during the acute phase and 2.42 h in remission. There were no pharmacokinetic differences between the patients who responded or did not respond to oral treatment. CONCLUSION: In children with inflammatory bowel disease, the initial response to corticosteroid therapy was not influenced by the pharmacokinetics of prednisolone and methylprednisolone. In addition, the pharmacokinetics of prednisolone was not modified by the inflammatory syndrome.

Acute-Phase Reaction↗
PubMed1997

N-conjugates of 2,5-disubstituted pyrrole and glutathione. Evaluation of their potency as antioxidants against photosensitization of NCTC 2544 keratinocytes by excess endogenous protoporphyrin IX.

A novel glutathione compound in which the amino group has been derivatized by a 2,5-dimethyl pyrrole is shown to be very effective against cell photosensitization in vitro. Protoporphyrin IX either added to the medium or produced endogenously by incubation of NCTC 2544 keratinocytes with 5-aminolevulinic acid has been chosen as the photosensitizer. The antioxidant effectiveness of glutathione-pyrrole derivatives against protoporphyrin photosensitization depends critically on the type of 2,5 substitution on the pyrrole ring. This structure-function relationship may be attributed to the difference in compartmentation and/or uptake of the various glutathione-pyrrole derivatives under study. The 2,5-dimethyl pyrrole derivative is much more effective than glutathione as a protective agent against phototoxic reactions induced by protoporphyrin IX.

Aminolevulinic Acid↗
PubMed1997

In vivo functional investigations of lactic acid in patients with respiratory chain disorders.

OBJECTIVE: To assess the prevalence of in vivo detectable abnormalities of lactate metabolism in mitochondrial disorders. DESIGN: Retrospective study in a metabolic investigation unit. PATIENTS: 28 patients with a respiratory chain disorder identified from biochemical or genetic analyses, or both, and 133 age matched controls. Controls were children in whom causes of secondary hyperlactataemia and/or disorders, affecting the energy pathways could be excluded. METHODS: Lactate and pyruvate were measured in blood, together with other intermediary metabolism indices, before and one hour after four meals each day. Lactate and creatinine in a 24 hour urine sample collected at the same time were analysed. When basal hyperlactataemia was not evident, an intravenous glucose or pyruvate loading test was performed as a provocative test. RESULTS: Abnormal lactate metabolism was found in 25 of 28 patients thus demonstrating the potential usefulness of these investigations in the diagnosis of mitochondrial disease. Moderate lactate accumulation was present in relatively mild disease, associated with a mitochondrial DNA mutation and combined respiratory complexes deficiency. By contrast, high lactate concentrations were observed in very young children, with severe disease, isolated complex deficiency, and no apparent mitochondrial DNA defect.

Adolescent↗
PubMed1997

[Criteria for quantification and characterization of aneurysms of the abdominal aorta using ultrasonography. The AFFCA study. French Association of Continuous Education in Angiology].

OBJECTIVE: To validate ultrasonographic quantification and characterization criteria for aneurysms of the abdominal aorta (AAA) by comparing computed tomography data and surgical findings in order to standardize diagnosis and follow-up of AAA. PATIENTS AND METHODS: A multicentric prospective study included 80 patients with AAA (January to August 1996). Standardized data on quantitative (diameter, surface area) and qualitative (topography, form, wall, thrombus) data were obtained at each ultrasound examination and at surgery. Ultrasound (US) and computed tomography (CT) explorations were performed and interpreted without prior knowledge by independent operators. US findings versus CT reference were compared in 77 cases, US findings versus surgical reference in 31, and CT findings versus surgery reference in 28. RESULTS: Compared with CT-scan, B mode ultrasound (n = 77) underestimated the anteroposterior diameter of the aneurysm (mean difference -2.16 mm; p < 0.001), the anteroposterior diameters of the flow channel lumen (-5.54 mm; p < 0.001) and upper neck of the aneurysm (-2.74 mm; p < 0.001). Surface area measurements were not significantly different both the aneurysmal sac (p = 0.3) and the flow channel lumen (p = 1). Compared with surgical findings, US (n = 30) underestimated the transverse diameter (mean difference (-4.29 mm; p = 0.0037). Compared with surgery, US findings (n = 28) were not significantly different for the anteroposterior ans transverse diameters. Analyzing the form and wall of the AAA, US/CT-scan performance was good for symmetrical fusiform aneurysms (sensitivity 77%, specificity 67%). US and CT-scan were reliable for detecting wall bugles (same sensitivity, 29%). The angle formed by the thrombus with the wall (expressed in degrees) was not significantly different (p = 0.9). When the lower pole of the aneurysm was situated above the aortic bifurcation, US (sensitivity 75%) was more reliable than the CT-scan (sensitivity 50%) compared with surgical findings. CONCLUSION: Ultrasonography should not be limited to the simple positive diagnosis of AAA. A precise analysis of the diameters and surface areas of the aneurysm should be performed.

Aged↗
PubMed1996

Morphological studies of skeletal muscle in lactic acidosis.

This paper underscores the contribution of routine morphological examination of skeletal muscle in patients with lactic acidosis. Mitochondrial disorders are by far the most common causes of primary lactic acidosis, in which muscle biopsy analysis helps in diagnosis and in the search for the molecular anomalies. Thus, we focus our attention on one particular point: the contribution of the morphological study of muscle biopsy in primary lactic acidosis due to mitochondrial disorders, especially mitochondrial respiratory-chain diseases.

Acidosis, Lactic↗
PubMed1996

Clinical and molecular heterogeneity of cytochrome c oxidase deficiency in the newborn.

We report 8 cases of severe cytochrome c oxidase deficiency with onset in the neonatal period. Clinical symptoms were heterogeneous: antenatal cerebral malformations, neurological distress with ketoacidosis, severe myopathy, or isolated respiratory control failure. Lactic acid was elevated in blood and/or CSF in 7 cases. Muscle biopsy (7 patients), liver biopsy (4 patients), and cultured skin fibroblasts (7 patients) were used to assess the cytochrome c oxidase deficiency. Among the patients, the enzymatic defect differed in the level of residual activity, expression in different tissues and subunit composition in muscle (as analysed by immunohistochemistry). Southern blot analysis of the mitochondrial DNA was normal in 7 patients. The heterogeneity of cytochrome c oxidase deficiency was therefore demonstrated by these clinical presentations and by the biochemical assessment of the enzyme defect. This reflects, most probably, the diverse nature of the causal mutations.

Cytochrome-c Oxidase Deficiency↗