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Biomedical subjects

J M Matthieu

Publications and source records attributed to J M Matthieu.

At least 19 recordsLinked to original sources
PubMed2001

Antibodies directed against rubella virus induce demyelination in aggregating rat brain cell cultures.

To link the presence of intrathecal virus-specific oligoclonal immunoglobulin G (IgG) in multiple sclerosis patients to a demyelinating activity, aggregating rat brain cell cultures were treated with antibodies directed against two viruses, namely, rubella (RV) and hepatitis B (HB). Anti-RV antibodies in the presence of complement decreased myelin basic protein concentrations in a dose-dependent manner, whereas anti-HB antibodies had no effect. A similar but less pronounced effect was observed on the enzymatic activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, which is enriched in noncompact membranes of oligodendrocytes. These effects were comparable to those in cultures treated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG), previously found to be myelinotoxic both in vitro and in vivo. Sequence homologies were found between structural glycoprotein E(2) of RV and MOG, suggesting that demyelination was due to molecular mimicry. To support the hypothesis that demyelination was caused by anti-RV IgG that recognized an MOG epitope, we found that anti-RV antibodies depleted MOG in a dose-dependent manner. Further evidence came from the demonstration that anti-RV and anti-MOG IgG colocalized on oligodendrocyte processes and that both revealed by Western blot a 28 kDa protein in CNS myelin, a molecular weight corresponding to MOG. These findings suggest that a virus such as RV exhibiting molecular mimicry with MOG can trigger an autoimmune demyelination.

Animals↗
PubMed2001

Implication of the extracellular disulfide bond on myelin protein zero expression.

Mutations in myelin protein zero (P0) are responsible for several peripheral neuropathies. We studied transport and membrane integration of the truncated P0 mutants using transfected oligodendroglial cell line (Oln93). Starting with rat cDNA, we produced two P0 deletions. The first, called P0-Tyr contains a 66 amino acid deletion in the extracellular domain and a tyrosine at the new position 32. In the second, called P0-Cys, the tyrosine 32 is replaced by a cysteine. This replacement restores a disulfide bond in the extracellular domain. Our results show that P0 proteins, truncated or not, were expressed in the plasma membrane of the transfected cells. Transcription rates of both mutants were normal. However, P0-Tyr was detected in only 3-5% of the cells compared to the P0-Cys and the wild type. Thus, the disulfide bond in the extracellular domain is important for stability and correct addressing of the P0 protein.

Animals↗
PubMed2001

Remyelination in vitro following protein kinase C activator-induced demyelination.

In previous work we found that mezerein, a C kinase activator, as well as basic fibroblast growth factor (FGF-2) induce demyelination and partial oligodendrocyte dedifferentiation in highly differentiated aggregating brain cell cultures. Here we show that following protein kinase C activator-induced demyelination, effective remyelination occurs. We found that mezerein or FGF-2 caused a transient increase in DNA synthesis following a pronounced decrease of the myelin markers myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase. Both oligodendrocytes and astrocytes were involved in this mitogenic response. Within 17 days after demyelination, myelin was restored to the level of the untreated controls. Transient mitotic activity was indispensable for remyelination. The present results suggest that myelinating oligodendrocytes retain the capacity to reenter the cell cycle, and that this plasticity is important for the regeneration of the oligodendrocyte lineage and remyelination. Although it cannot be excluded that a quiescent population of oligodendrocyte precursor cells was present in the aggregates and able to proliferate, differentiate and remyelinate, we could not find evidence supporting this view.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2001

[Hyperaminoaciduria in children].

Hyperaminoaciduria is a major disorder to be considered in the event of growth and mental retardation, convulsion and other unexplained clinical symptoms. This review should enable the general practitioner to determine the conditions necessitating urinary and blood amino acid analyses in order to improve the treatment of children presenting rare pathologies, the prognosis of whom depends on the rapidity of the intervention. The diagnosis and treatment of hereditary and renal hyperaminoaciduria are discussed and a physiological and physiopathological synthesis of the tubular reabsorption of amino acids is presented. The different clinical entities associated with hyperaminoaciduria are then briefly described according to their origin (renal or prerenal).

Child↗
PubMed2001

[Maternal phenylketonuria].

The child of a phenylketonuric woman is exposed during pregnancy to a high risk of growth retardation and malformation. The frequency of these abnormalities is proportional to the maternal phenylalanine blood concentrations. If a strict low protein diet is followed before conception and throughout gestation the risks of abnormalities are not higher than in the normal population. The maternal blood phenylalanine levels must be maintained between 120 and 250 mumol/l and the tyrosine blood levels between 45 and 90 mumol/l. Weekly blood analyses are mandatory. Regular dietary controls are necessary to assure that the adequate energetic intake and the correct amounts of vitamins and minerals recommended for a pregnant woman are sustained. A case report is the opportunity to discuss certain practical aspects concerning the monitoring of the pregnancy of a phenylketonuric woman and to make general recommendations.

Adult↗
PubMed2001

[Mitral valve prolapse and type II mucopolysaccharidosis. Report of two familial cases].

Type II mucopolysaccharidosis (Hunter's disease) is a hereditary condition due to a deficit of a lysosome specific hydrolase (iduronate sulfatase) inducing an accumulation of dermatane-sulphate and heparane-sulphate in certain organs. Cardiac involvement is constant in this disease and manifests itself essentially by aortic valve stenosis and insufficiency and/or mitral insufficiency which is progressive, irreversible and life-threatening. Two brothers of Portuguese nationality suffering from a so-called slight form of this disease had classical mucopolysaccharide infiltration of their aortic valves. The elder brother, aged 11, had severe aortic insufficiency associated with mild stenosis requiring treatment with vasodilator drugs. The younger, aged 8, had asymptomatic mild aortic regurgitation. Curiously, mitral valve prolapse with regurgitation was present in both children. The association of mitral valve prolapse and type II mucopolysaccharidosis, without other typical cardiac involvement, has only been reported once in the literature.

Age of Onset↗
PubMed1999

Long-term effects of neonatal hypoglycemia on brain growth and psychomotor development in small-for-gestational-age preterm infants.

OBJECTIVE: To investigate the effects of neonatal hypoglycemia on physical growth and neurocognitive function. STUDY DESIGN: A systematic detection of hypoglycemia (<2.6 mmol/L or 47 mg/dL) was carried out in 85 small-for-gestational-age preterm neonates. Prospective serial evaluations of physical growth and psychomotor development were performed. Retrospectively, infants were grouped according to their glycemic status. RESULTS: The incidence of hypoglycemia was 72.9%. Infants with repeated episodes of hypoglycemia had significantly reduced head circumferences and lower scores in specific psychometric tests at 3.5 years of age. Hypoglycemia also caused reduced head circumferences at 18 months and lower psychometric scores at 5 years of age. Infants with moderate recurrent hypoglycemia had lower scores at 3.5 and 5 years of age compared with the group of infants who had 1 single severe hypoglycemic episode. CONCLUSION: Recurrent episodes of hypoglycemia were strongly correlated with persistent neurodevelopmental and physical growth deficits until 5 years of age. Recurrent hypoglycemia also was a more predictable factor for long-term effects than the severity of a single hypoglycemic episode. Therefore repetitive blood glucose monitoring and rapid treatment even for mild hypoglycemia are recommended for small-for-gestational-age infants in the neonatal period.

Blood Glucose↗
PubMed1999

Analysis of cis-acting sequences from the myelin oligodendrocyte glycoprotein promoter.

Myelin oligodendrocyte glycoprotein (MOG), a minor component of the myelin sheath, appears to be implicated in the late events of CNS myelinogenesis. To investigate the transcriptional regulation of MOG, 657 bp of the 5'-flanking sequence of the murine MOG gene, previously shown to induce the highest level of transcription in an oligodendroglial cell line, was analyzed by in vitro footprinting and electrophoretic mobility shift assays. This region contains at least three sites that contact nuclear proteins in vitro. Each region described in this study binds specific nuclear proteins and enhances transcription in the OLN-93 glial cell line. More specifically, a region located at position -93 to -73 bp, which displays 100% homology in mouse and human MOG promoters, presents distinct binding affinities between brain and liver nuclear proteins. The results obtained by supershift assay and site-directed mutagenesis reveal that this region contains an essential positive element (TGACGTGG) related to the cyclic AMP-responsive element CREB-1 and are additional evidence for the involvement of the cyclic AMP transduction pathway in oligodendrocyte development.

Animals↗
PubMed1999

The naturally occurring food mycotoxin fumonisin B1 impairs myelin formation in aggregating brain cell culture.

The effects of subchronical applications of the mycotoxin Fumonisin B1 (FB1) were analyzed in vitro, using aggregating cell cultures of fetal rat telencephalon as a model. As cells in the aggregates developed from an immature state to a highly differentiated state, with synapse and compact myelin formation, it was possible to study the effects of FB1 at different developmental stages. The results showed that FB1 did not cause cell loss and it had no effects on neurons. However it decreased strongly the total content of myelin basic protein, the main constituent of the myelin sheath, during the myelination period (DIV 18-28). The loss of myelin was not accompanied by a loss of oligodendrocytes, the myelinating cells. However FB1 had effects on the maturation of oligodendrocytes, as revealed by a decrease in the expression of galactocerebroside, and on the compaction of myelin, as shown by a reduction of the expression of the mnyelin/oligodendrocyte glycoprotein MOG. The content of the cytoskeletal component glial fibrillary acidic protein (GFAP) was decreased in differentiated astrocytes, exclusively, while neurons were not affected by 40 microM of FB1 applied continuously for 10 days. In summary, FB1 selectively affected glial cells. In particular, FB1 delayed oligodendrocyte development and impaired myelin formation and deposition.

Animals↗
PubMed1998

Myelin basic protein immunoreactivity in the human embryonic CNS.

Myelin basic protein (MBP) is a major myelin constituent produced by oligodendrocytes in the central nervous system (CNS). Expression of MBP was considered to be a marker for oligodendrocyte differentiation and myelination in the developing CNS. In this study, expression of myelin basic protein (MBP) and its messenger RNA (mRNA) was examined in human embryos and fetuses ranging in age from 5 to 20 gestational weeks (g.w.). We were able to demonstrate that MBP antibody labels cells in both human nervous and non-nervous tissues beginning from early embryonic life (5-6 g.w.). MBP positive (MBP+) cells were rounded, with either no cell processes or only 1-2 short processes, and were located in caudal regions of the CNS. MBP+ cells were also observed in the non-nervous tissue, such as leptomeninges, choroid plexus, and connective tissues. A number of MBP+ cells in nervous and non-nervous tissues were morphologically similar to macrophages and showed a positive reaction to macrophage-microglia markers: lectin (RCA-1) and the monoclonal antibody (EBM-11) to human macrophage antigen CD68, whereas they were negative for neuronal, astroglial, or marker for oligodendrocyte progenitors. At the same embryonic age, 5 g.w. and onward, the MBP mRNA was observed in the CNS by in situ hybridization. The results of this study show that MBP immune reaction is spread in a large area of the CNS prior to myelin appearance. In addition, for the first time it has been demonstrated that the same population of cells could be labelled with both MBP and macrophage markers. These results indicate that MBP, or MBP-related proteins, could represent a link between the immune and nervous system during early development. Thus, besides the well established role in myelination, these proteins might have an additional and still unknown function in development.

Central Nervous System↗
PubMed1998

Familial cardiomyopathy and distal myopathy with abnormal desmin accumulation and migration.

Desminopathies form a heterogeneous group of myopathies characterised by pathological aggregations of desmin. We report a family, where mother and daughter presented with an atrioventricular block and a slowly progressive distal muscular weakness, with non-homogeneous focal atrophy on computed tomography scans. The mother developed a severe global heart insufficiency necessitating a heart transplantation at 56 years of age. Skeletal muscle biopsies were characterised by inclusion bodies strongly expressing desmin and alpha B-crystallin, with a predominantly subsarcolemmal localisation. Ultrastructurally most inclusions corresponded to non-membrane bound granulo-filamentous material with disruption of myofibrils. An immunoblot showed a hyperintense desmin band at 53 kDa and a second band at 49 kDa, the latter being absent in controls. The cardiac muscle of the explanted heart showed very similar inclusions. These cases illustrate that in this distinct subtype of desminopathies the cardiac muscle alterations are comparable with those observed in skeletal muscle, and suggest the possibility of a primary desmin pathology.

Adult↗
PubMed1997

Intracellular transport of the DM-20 bearing shaking pup (shp) mutation and its possible phenotypic consequences.

Paralytic tremor (pt) in rabbits and shaking pup (shp) in dogs are allelic dysmyelinated mutants of the proteolipid protein (Plp) gene. Both mutations affect the same amino acid, histidine36, which is replaced by glutamine in pt and by proline in shp. Phenotypic expression of these two mutations is very different. Paralytic tremor presents a much milder form of dysmyelination than shaking pup. The number of oligodendrocytes in the mutant rabbit is normal, while in the dog, the oligodendrocyte number is reduced due to early death or incomplete maturation. We have previously reported an abnormal intracellular transport of the PLPpt, whereas DM-20pt was normally transported to the cell membrane. In the present study, we show that the transport of the two isoforms containing the shp mutation is impaired in transfected Cos-7 cells. Cotransfecting cells with different ratios and combinations of mutated PLP and DM-20 cDNAs, we demonstrated that DM-20pt, but not DM-20shp, facilitates intracellular trafficking and integration into the plasma membrane of either of the two mutated PLPs. The phenotypic difference between these two allelic mutations can result from differences in DM-20 protein trafficking and sorting. These results show that the loss of function of PLP is not position-dependent but depends on the nature of the mutation.

Animals↗
PubMed1997

Demyelination induced by protein kinase C-activating tumor promoters in aggregating brain cell cultures.

The plasticity of mature oligodendrocytes was studied in aggregating brain cell cultures at the period of maximal expression of myelin marker proteins. The protein kinase C (PKC)-activating tumor promoters mezerein and phorbol 12-myristate 13-acetate (PMA), but not the inactive phorbol ester analog 4alpha-PMA, caused a pronounced decrease of myelin basic protein (MBP) content and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity. In contrast, myelin/oligodendrocyte protein (MOG) content was affected relatively little. Northern blot analyses showed a rapid reduction of MBP and PLP gene expression induced by mezerein, and both morphological and biochemical findings indicate a drastic loss of compact myelin. During the acute phase of demyelination, only a relatively small increase in cell death was perceptible by in situ end labeling and in situ nick translation. Basic fibroblast growth factor (bFGF) also reduced the levels of the oligodendroglial differentiation markers and enhanced the demyelinating effects of the tumor promoters. The present results suggest that PKC activation resulted in severe demyelination and partial loss of the oligodendrocyte-differentiated phenotype.

Animals↗
PubMed1996

An antisense transgenic strategy to inhibit the myelin oligodendrocyte glycoprotein synthesis.

To understand the function of the myelin oligodendrocyte glycoprotein (MOG), a myelin specific protein of the central nervous system, transgenic mice were produced. The transgene is a fusion gene containing 1.9 kb of murine myelin basic protein promoter, 430 bp of rat MOG cDNA in the reverse orientation and 4.5 kb of human proteolipid protein gene. In spite of high expression of antisense MOG mRNA in the oligodendrocytes, MOG synthesis was not inhibited in transgenic mice. This lack of inhibition of MOG underlines the difficulties encountered with antisense transgenic strategies.

Animals↗
PubMed1996

Selective toxicity of the general anesthetic propofol for GABAergic neurons in rat brain cell cultures.

The intravenous, short-acting general anesthetic propofol was applied to three-dimensional (aggregating) cell cultures of fetal rat telencephalon. Both the clinically used formulation (Disoprivan, ICI Pharmaceuticals, Cheshire, England) and the pure form (2,6-diisopropylphenol) were tested at two different periods of brain development: immature brain cell cultures prior to synaptogenesis and at the time of intense synapses and myelin formation. At both time periods and for clinically relevant concentrations and time of exposure (i.e., concentrations > or = 2.0 micrograms/ml for 8 hr), propofol caused a significant decrease of glutamic acid decarboxylase activity. This effect persisted after removal of the drug, suggesting irreversible structural changes in GABAergic neurons. The gamma-aminobutyric acid type A (GABAA) blocking agents bicuculline and picrotoxin partially attenuated the neurotoxic effect of propofol in cultures treated at the more mature phase of development. This protective effect was not observed in the immature brain cells. The present data suggest that propofol may cause irreversible lesions to GABAergic neurons when given at a critical phase of brain development. In contrast, glial cells and myelin appeared resistant even to high doses of propofol.

Anesthetics, General↗
PubMed1996

Myelin/oligodendrocyte glycoprotein (MOG) expression is associated with myelin deposition.

We investigated the onset of expression of the myelin/oligodendrocyte glycoprotein (MOG) mRNA and protein in the developing mouse central nervous system. In situ hybridization on brain sections at different stages of embryonic and postnatal development showed that MOG transcripts were first detected at birth in the medulla oblongata. During the first week after birth, cells expressing MOG mRNA were located in the ventral longitudinal funiculus. During the second postnatal week, the pattern of MOG mRNA expression extended rostrally to the mid-forebrain regions and reached completion by the beginning of the third week. MOG transcription was delayed by several days with respect to myelin basic protein (MBP), and it appeared that while the MBP probe labeled both non-myelinating and myelinating oligodendrocytes, only the latter were MOG-positive. In vitro, immunocytochemical analysis of MOG protein expression, performed on myelinating cultures derived from mouse brain embryos at 15 days of gestation, confirmed the strict restriction of MOG expression to myelinating oligodendrocytes. In particular, oligodendrocytes lining up their processes along axons, but not yet having started to deposit a myelin sheath, were still MOG negative. However, in the same cultures, pseudo-myelinating oligodendrocytes (i.e., cells not associated with neurites, but forming whorls of myelin-like figures) were MOG positive. Similarly, rat CG4 cells, an oligodendrocyte-like cell line, expressed MOG only after they had extended sheet-like processes, which suggested that the activation of MOG transcription depends more on an intrinsic oligodendroglial maturation program of myelination than on a neuronal signal.

Animals↗
PubMed1996

Proteolipid/DM-20 proteins bearing the paralytic tremor mutation in peripheral nerves and transfected Cos-7 cells.

Paralytic tremor (Plp-pt) is a missense mutation of the myelin proteolipid gene (Plp) in rabbits. The myelin yield in the Plp-pt brain is reduced and the protein and lipid composition of central nervous system (CNS) myelin is abnormal. We studied the intracellular transport of the normal and Plp-pt mutant PLP and DM-20 in transiently transfected Cos-7 cells. While the mutant PLP accumulates in the rough endoplasmic reticulum and does not reach the plasma membrane, the spliced isoform of PLP, mutant DM-20, is normally transported to the cell surface and integrated into the membrane. Analysis of rabbit sciatic nerves revealed that concentration of peripheral nervous system (PNS) myelin proteins is normal in Plp-pt myelin. In the PNS like in the CNS, the level of Plp gene products is subnormal. But this does not affect myelination in the PNS where PLP, present in low concentration, is not a structural component of compact myelin. The normal level of Plp gene expression in Schwann cells is low and these results suggest that, in the Plp-pt PNS, Schwann cell function is not affected by the deficiency in PLP and/or the impairment of intracellular PLP transport.

Animals↗