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M Mathieu

Publications and source records attributed to M Mathieu.

At least 127 records · Page 7Linked to original sources
PubMed1995

Cloning and characterization of the neural isoforms of human dystonin.

Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that leads to a sensory ataxia. We have identified and cloned a gene encoded at the dt locus. The product of the dt gene, dystonin, is a neural isoform of a hemidesmosomal protein bullous pemphigoid antigen 1 (bpag1). To investigate the potential role of dystonin in human neuropathies, we have cloned the neural-specific 5' exons of the human DT gene that together with the previously cloned BPAG1 sequences comprise human dystonin. The mouse and human dystonin genes demonstrate the same spectrum of alternatively spliced products, and the amino acid sequences of the neural-specific exons in the mouse and human genes are over 96% identical.

Amino Acid Sequence↗
PubMed1995

The basal level of transcription of the alc genes in the ethanol regulon in Aspergillus nidulans is controlled both by the specific transactivator AlcR and the general carbon catabolite repressor CreA.

In the A. nidulans ethanol utilization pathway, specific induction is mediated by the transactivator AlcR which is subject to strong positive autogenous regulation and activates the transcription of the two structural genes alcA and aldA. Carbon catabolite repression is mediated by CreA which represses directly the transacting gene alcR and the two structural genes. We show here that the basal expression of the alcR and alcA genes is also controlled by the two regulatory circuits, positively by the transactivator AlcR and negatively by the repressor CreA, the aldA gene being subject only to the control of the CreA repressor.

Aspergillus nidulans↗
PubMed1995

Processing of iduronate 2-sulphatase in human fibroblasts.

Iduronate 2-sulphatase (IDS) is a lysosomal enzyme involved in degradation of dermatan sulphate and heparan sulphate. Antigenic material was obtained either by purification of placental IDS (A and B forms) or by expression of three different fusion peptides in Escherichia coli allowing the production of five specific antibodies. Pulse-chase-labelling experiments in over-expressing fibroblasts showed poor IDS processing but large amounts of precursors were secreted into the medium. The endocytosis of the 35S- or 33P-labelled precursors by deleted fibroblasts together with glycosylation studies and proteolysis inhibition by leupeptin allowed better elucidation of IDS maturation. The initial 73-78 kDa form is converted into a phosphorylated 90 kDa precursor after modification of its oligosaccharide chains in the Golgi apparatus. This precursor is processed by proteolytic cleavage through various intermediates to a major 55 kDa intermediate, with the release of an 18 kDa polypeptide. Further proteolytic cleavage by a thiol protease gives the 45 kDa mature form containing hybrid and complex-type oligosaccharide chains.

Base Sequence↗
PubMed1995

Fibroblast growth factor (FGF) 3 from Xenopus laevis (XFGF3) binds with high affinity to FGF receptor 2.

We demonstrate that purified fibroblast growth factor (FGF) 3 from Xenopus laevis (XFGF3) activates the mitogen-activated protein kinase pathway and induces DNA synthesis in quiescent cells. To characterize the high affinity cell surface receptors that mediate these responses, the ligand binding domains of different FGF receptors (FGFR) were expressed on COS-1 cells, and their affinity for XFGF3 was determined. Unlabeled XFGF3 efficiently competed with 125I-FGF1 for binding to the IIIb and IIIc isoforms of FGFR2, giving 50% displacement (ID50) at 0.3-0.8 nM. Higher XFGF3 concentrations were needed to displace 125I-FGF1 from FGFR3 and FGFR1 (ID50 approximately 4 and 21 nM, respectively), indicating that XFGF3 has a lower affinity for these receptors. No association of XFGF3 with FGFR4 was found using this assay. FGFR2 isoforms isolated from both mouse and Xenopus showed similar high affinity binding of XFGF3 as determined by direct binding assays (Kd values in the range of 0.2-0.6 nM). These results indicate that the binding specificity of XFGF3 is different from that of other FGFs, and identifies FGFR2 as its high affinity receptor.

Amino Acid Sequence↗
PubMed1995

Dystonin expression in the developing nervous system predominates in the neurons that degenerate in dystonia musculorum mutant mice.

Dystonia musculorum (dt) is an inherited neurodegenerative disorder in mice. The dt gene product, dystonin, contains the bullous pemphigoid antigen 1 coding region at its C-terminus and an actin binding domain at its N-terminus. We demonstrate that dystonin expression throughout mouse development predominates in neurons of the cranial and spinal sensory ganglia. These structures are the most severely affected in dystonic mice which could explain their severe sensory ataxia. Since we show expression in sensory neurons with small and large axoplasmic volumes, but degeneration is restricted primarily to the latter type, we suggest that caliber and size of the axon is an important factor in the disease process. Dystonin is also expressed in the extrapyramidal motor system and in the cerebellum. Functional defects in these cell types could account for the dystonic symptoms of dt mice not explained by simple sensory denervation. We also detect dystonin expression in motor neurons most of which are unaffected by the degenerative process in dt mice.

Animals↗
PubMed1995

Fine mapping of randomly distributed multiple deletions of mitochondrial DNA in a case of chronic progressive external ophthalmoplegia.

Multiple deletions of mitochondrial DNA have been detected by Southern blotting in the skeletal muscle of a 42-year-old woman with chronic progressive external ophthalmoplegia. A PCR method, using several combinations of primers covering the whole mtDNA as well as sequence analysis, disclosed the wide spectrum of these multiple deletions differing in size, location and sequence at the breakpoint junction. Most involved the major region between the two replication origins. However, three deletions affected the minor region and lacked either the light strand origin of replication or the heavy strand promoter. These data suggest an impairment of mtDNA replication leading to illegitimate recombination and extensive damage of mtDNA.

Adolescent↗
PubMed1995

Immunohistochemical localization of FMRFamide-containing neurons and nerve fibers in the ganglia and the gonad wall of the scallop, Pecten maximus (L).

The Phe-Met-Arg-Phe NH2 (FMRFamide)-like immunoreactivity was detected in neurons of the cerebro-pedal and visceral ganglia of the scallop Pecten maximus using immunohistochemical techniques. FMRFamide-like immunoreactivity was also found in nerve fibers localized in the connective tissue and the epithelial wall of the gonad. Electron microscopy study carried out on the gonads indicates the existence of numerous nerve fibers crossing the connective tissue; nerve terminals apposed to highly secretory cells were seen in the gonad wall. All in all, the present immunohistochemical and electron microscopic data suggest that FMRFamide might play an unusual secretagogue role in the gonad wall.

Animals↗
PubMed1995

[Mycobacterium kansasii infection in patients with human immunodeficiency virus infection].

We report a retrospective study of 12 caucasian men infected with HIV who had developed Mycobacterium kansasii infection (Mk). All patients had a low blood lymphocyte CD4 count (1-130, mean 15/mm3) and ten met the diagnostic criteria for AIDS. The 12 patients had pulmonary symptoms (dyspnea, cough) and fever. On chest X-ray, nodular, interstitial or diffuse parenchymal infiltrates, mediastinal and hilar adenopathies were observed. Two patients had pleural effusion, but none had cavitary lung disease. Mk was isolated by culture of sputum (n = 7), blood (n = 3), bronchial biopsy (n = 2) or bone marrow (n = 1). No patient had clinical extra-pulmonary disease. Survival after diagnosis was in average 7 months. Potential for therapeutic response is reviewed and documented.

AIDS-Related Opportunistic Infections↗
PubMed1995

The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1.

Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that leads to a sensory ataxia. We describe cloning of a candidate dt gene, dystonin, that is predominantly expressed in the dorsal root ganglia and other sites of neurodegeneration in dt mice. Dystonin encodes an N-terminal actin binding domain and a C-terminal portion comprised of the hemidesmosomal protein, bullous pemphigoid antigen 1 (bpag1). dt and bpag1 are part of the same transcription unit which is partially deleted in a transgenic strain of mice, Tg4, that harbours an insertional mutation at the dt locus, and in mice that carry a spontaneous dt mutation, dtAlb. We also demonstrate abnormal dystonin transcripts in a second dt mutant, dt24J. We conclude that mutations in the dystonin gene are the primary genetic lesion in dt mice.

Amino Acid Sequence↗
PubMed1995

An abnormal exercise test response revealing a respiratory chain complex III deficiency.

A 29-year-old man with a progressive exertional muscle intolerance since childhood was referred for incremental exercise test on a bicycle ergometer. The response pattern suggested a mitochondrial myopathy: that is, a greatly reduced maximum oxygen consumption with appropriate heart rate increase and an anaerobic threshold point reached early. The metabolic investigation in plasma revealed an abnormal oxidoreduction status (hyperlactataemia and high lactate/pyruvate ratio) at rest and after a carbohydrate rich meal. The histochemical examination of a muscle biopsy revealed red granular deposits under the sarcolemma for all type 1 fibers. Oxypolarographic and enzymological studies of the mitochondrial respiratory chain in both isolated mitochondria and muscle homogenate demonstrated a marked deficiency of ubiquinol cytochrome c reductase (complex III) activity.

Adult↗
PubMed1995

Inspiratory fall in systolic pressure in normal and asthmatic subjects.

We used a noninvasive monitor of arterial pressure to determine whether respiratory changes in arterial pressure were closely correlated with airflow obstruction in asthmatic patients during bronchial challenge with methacholine. To validate the noninvasive measurement of respiratory changes in arterial pressure, a preliminary study in 6 subjects with normal cardiovascular and respiratory systems was done during cardiac catheterization for suspected coronary artery disease. There were no significant differences between inspiratory falls in systolic pressure measured noninvasively and those measured from intraaortic pressure. In 11 otherwise healthy asthmatic patients we measured finger arterial pressure, end-expiratory lung volume (FRC), and forced expired volume (FEV1) during baseline and bronchial challenge in the supine posture. Finger arterial pressure was also measured in 11 normal control subjects seated and supine. Normal subjects had an inspiratory fall in systolic pressure (IFSP) of 3.2 mm Hg supine and 5.1 mm Hg seated (p < 0.01). Asthmatic patients when bronchodilated (seated FEV1 = 83 +/- 7% of predicted) had an IFSP of 5.9 mm Hg supine (p < 0.01 compared with supine normal subjects). During bronchial challenge (average fall in FEV1 = 22%), IFSP increased to 16.1 mm Hg (p < 0.001 compared with baseline). In asthmatic subjects, there was a significant correlation between IFSP and FEV1 (mean r = -0.92 +/- 0.05, p < 0.01), and the average change in IFSP/change in FEV1 was -0.38 mm Hg per percentage change in FEV1. During subsequent bronchodilation, IFSP decreased with a similar time course as relaxation of airway smooth muscle, assessed by the breath-to-breath fall in FRC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Serum 5'-nucleotidase and alkaline phosphatase activities after high dose chemotherapy and bone marrow transplantation in cases of malignancy in children.

After bone marrow transplantation in children, it is essential to detect secondary liver diseases and hepatotoxic effects of immunosuppressive therapy. These can be revealed by cytolytic syndromes sometimes associated with cholestasis. It is therefore important to find an early and specific cholestasis enzymatic marker. A retrospective study of the changes in levels of biological parameters has been carried out in 13 children who underwent one or more bone marrow transplantations. During the 3 months following bone marrow transplantation, all patients developed liver injury characterized by an early and very elevated 5'-nucleotidase activity (sometimes more than 40 times the upper reference limit), a moderate increase in alkaline phosphatase activity, a variable increase in alanine aminotransferase activity and inconstant changes in total bilirubin levels. These results show that cytolytic syndrome and cholestasis are often associated with increases in 5'-nucleotidase and alkaline phosphatase activities. These increases are not correlated, probably due to the influence of therapy on the synthesis and release of both enzymes in the liver. 5'-nucleotidase seems to be the best marker for the detection and follow-up of liver disease in this patient group.

5'-Nucleotidase↗