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Biomedical subjects

B Fontaine

Publications and source records attributed to B Fontaine.

At least 91 records · Page 5Linked to original sources
PubMed1999

Evaluation of a capillary electrophoresis method for routine determination of hemoglobins A2 and F.

Hemoglobin A2 (Hb A2) and hemoglobin F (Hb F) are important analytes in the diagnosis and follow up of Hb diseases. We evaluated a new capillary zone electrophoresis (CZE) kit for Hb A2 and Hb F measurements. The imprecision ranged from 3% to 6% for Hb A2 and Hb F at physiological and pathological concentrations. The method compared well with cation-exchange HPLC for Hb A2 and Hb F and with anion-exchange chromatography in microcolumns (MAEC), for Hb A2. Nevertheless, higher results were obtained [Hb A2 CZE (%) = 1.233 Hb A2 HPLC - 0.2; Hb A2 CZE (%) = 1.190 Hb A2 MAEC + 0.1; Hb FCZE (%) = 1.118 Hb FHPLC + 0.4], and new reference values had to be determined (Hb A2 2.7-3.8%; Hb F <1.2%). Quantification of Hb A2 was not influenced by Hb S. Measurement of Hb F was accurate and precise except at low concentrations in Hb AS patients. This new CZE kit is rapid, precise, and reliable, and seems appropriate for use in clinical laboratories.

Electrophoresis, Capillary↗
PubMed1998

Apolipoprotein E and multiple sclerosis: a biochemical and genetic investigation.

Apolipoprotein E (apo E) is postulated to be a major lipid carrier protein in the brain involved in brain development and repair. Multiple sclerosis (MS) is a major demyelinating disease characterized by destruction of myelin and marked alteration of myelin cholesterol and lipid metabolism. We have determined serum and cerebrospinal fluid (CSF) apo E concentrations using an original time-resolved immunofluorometric assay and calculated intrathecal apo E concentration. Apo E concentrations were determined in 13 control subjects and 129 neurological patients: 34 definite MS patients, 25 with Guillain-Barré syndrome (GBS), 32 with amyotrophic lateral sclerosis (ALS) and 38 with other neurological diseases. Seven clinical parameters (sex, age, age at MS onset, duration of the disease, course, clinical status and disability score) were considered in MS patients. Significant (P < 0.01) decrease in CSF apo E was observed in MS, linked to a decrease in intrathecal apo E. The decreased CSF apo E concentration in MS patients occur independent of the apo E genotype. Apo E is considered as a neurotrophic factor in the brain. Any decrease in intrathecal apo E synthesis would thus contribute to progression of neurological diseases, such as MS.

Adult↗
PubMed1998

Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.

Hereditary spastic paraplegia (HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. We found that patients from a chromosome 16q24.3-linked HSP family are homozygous for a 9.5 kb deletion involving a gene encoding a novel protein, named Paraplegin. Two additional Paraplegin mutations, both resulting in a frameshift, were found in a complicated and in a pure form of HSP. Paraplegin is highly homologous to the yeast mitochondrial ATPases, AFG3, RCA1, and YME1, which have both proteolytic and chaperon-like activities at the inner mitochondrial membrane. Immunofluorescence analysis and import experiments showed that Paraplegin localizes to mitochondria. Analysis of muscle biopsies from two patients carrying Paraplegin mutations showed typical signs of mitochondrial OXPHOS defects, thus suggesting a mechanism for neurodegeneration in HSP-type disorders.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1998

Functional expression of the Ile693Thr Na+ channel mutation associated with paramyotonia congenita in a human cell line.

1. The Ile693Thr mutation of the skeletal muscle Na+ channel alpha-subunit is associated with an unusual phenotype of paramyotonia congenita characterized by cold-induced muscle weakness but no stiffness. This mutation occurs in the S4-S5 linker of domain II, a region that has not been previously implicated in paramyotonia congenita. 2. The Ile693Thr mutation was introduced into the human skeletal muscle Na+ gene for functional expression in human embryonic kidney (HEK) cells. The currents expressed were recorded with the whole-cell voltage-clamp technique. 3. In comparison with wild-type currents, Ile693Thr mutant currents showed a clear shift of about -9 mV in the voltage dependence of activation. 4. In contrast to other mutations of the Na+ channel known to cause paramyotonia congenita, the Ile693Thr mutation did not induce any significant change in the kinetics, nor in the voltage dependence, of fast inactivation. 5. In conclusion, this study provides further evidence of the involvement of the S4-S5 linker in the voltage dependence of Na+ channel activation. The negative shift in the voltage dependence found in this mutation must be associated to other defects, plausibly an impairment of the slow inactivation, to account for the long periods of muscle weakness experienced by the patients.

Cell Line↗
PubMed1998

Calcium currents and transients of native and heterologously expressed mutant skeletal muscle DHP receptor alpha1 subunits (R528H)

Rabbit cDNA of the alpha1 subunit of the skeletal muscle dihydropyridine (DHP) receptor was functionally expressed in a muscular dysgenesis mouse (mdg) cell line, GLT. L-type calcium currents and transients were recorded for the wild type and a mutant alpha1 subunit carrying an R528H substitution in the supposed voltage sensor of the second channel domain that is linked to a human disease, hypokalemic periodic paralysis. L-type channels expressed in GLT myotubes exhibited currents similar to those described for primary cultured mdg cells injected with rabbit wild type cDNA, indicating this system to be useful for functional studies of heterologous DHP receptors. Voltage dependence and kinetics of activation and inactivation of L-type calcium currents from mutant and wild type channels did not differ significantly. Intracellular calcium release activation measured by fura-2 microfluorimetry was not grossly altered by the mutation either. Analogous measurements on myotubes of three human R528H carriers revealed calcium transients comparable to controls while the voltage dependence of both activation and inactivation of the L-type current showed a shift to more negative potentials of approximately 6 mV. Similar effects on the voltage dependence of the fast T-type current and changes in the expression level of the third-type calcium current point to factors not primarily associated with the mutation perhaps participating in disease pathogenesis.

Animals↗
PubMed1998

Systemic autoimmune features and multiple sclerosis: a 5-year follow-up study.

OBJECTIVES: To evaluate in patients with multiple sclerosis (MS) the occurrence of clinical systemic signs and biological autoimmune abnormalities, including positive titers of antinuclear antibodies and antiphospholipid antibodies, suggestive of autoimmune diseases that may affect the central nervous system. Also, to compare the clinical and magnetic resonance imaging features and evolution of MS in patients with and without autoimmune abnormalities. DESIGN AND PATIENTS: Prospective study of 161 patients fulfilling the criteria of having probable or definite MS hospitalized in our institution between November 1990 and June 1992. RESULTS: Among the 161 patients, 84 (52.1%) had at least 1 clinical and/or biological general sign suggestive of an autoimmune disease; 64 were followed up for 4 to 5 years. The diagnosis of MS was confirmed in 50 patients and is still pending in 14 of them. No significant difference was found between patients with MS who were free of autoimmune features and those with autoimmune abnormalities (MS plus) concerning the age of disease onset, the presenting symptoms and signs, symptoms found on neurologic examination, and the course of the disease. For all patients with confirmed MS, general signs were found in 13.3%, positive titers of antinuclear antibodies in 26%, and positive titers of antiphospholipid antibodies in 6.2%. CONCLUSIONS: Patients with MS with autoimmune features, including those with titers of antinuclear antibodies of 1:100 or less and/or antiphospholipid antibodies, are not different than others with MS, and therefore should not be excluded from clinical trials.

Adolescent↗
PubMed1998

[Four hours for a record, or a severe fuminating cellulitis: can Saccharomyces cerevisiae be the causal agent?].

A 31-year-old woman presented with a subcutaneous cellulitis which occurred within four hours following a minor wound of a knee. This very short delay could be explained neither by the health state, nor the mechanism of injury, nor the bacteria usually responsible for such a cellulitis. Considering the clinical characteristics (high gas production) and the professional context (wine cellar employee), Saccharomyces cerevisiae, a yeast used for wine or bread production, may explain this complication.

Adult↗
PubMed1998

ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependence.

Mutations in the ClC-1 muscle chloride channel cause either recessive or dominant myotonia congenita. Using a systematic screening procedure, we have now identified four novel missense mutations in dominant (V286A, F307S) and recessive myotonia (V236L, G285E), and have analysed the effect of these and other recently described mutations (A313T, I556N) on channel properties in the Xenopus oocyte expression system. Mutations V286A, F307S and A313T displayed a 'classical' dominant phenotype: their voltage dependence was shifted towards positive potentials and displayed a dominant-negative effect by significantly imparting a voltage shift on mutant-wild-type heteromeric channels as found in heterozygous patients. In contrast, the recessive mutation V236L also shifted the voltage dependence to positive values, but co-expression with wild-type ClC-1 gave almost wild-type currents. I556N, a mutation found in patients with benign dominant myotonia, drastically shifts the voltage dependence, but only a slight shift is seen when co-expressed with wild-type ClC-1. Thus, the voltage dependence of mutant heteromeric channels is not always intermediate between those of the constituent homomeric channel subunits, a conclusion further supported by mixing different ClC-1 mutants. These complex interactions correlate clinically with various inheritance patterns, ranging from autosomal dominant with various degrees of penetrance to autosomal recessive.

Amino Acid Sequence↗
PubMed1998

Recent advances in immunology in multiple sclerosis.

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system that is of possible autoimmune origin. This article is divided into three parts, reviewing recent advances in three selected topics regarding the immunology of multiple sclerosis. The first part addresses the consequences of T cell and oligodendrocyte death in the inflammatory lesions. The second covers the recent experimental evidence favouring the involvement of infectious agents in the pathophysiology of central nervous system autoimmune diseases. The third part concerns the mode of action of interferon-beta in multiple sclerosis. These new advances have lead to a better understanding of the immunopathology of multiple sclerosis and therefore open new therapeutic possibilities.

Cell Death↗
PubMed1998

Quality assessment of whole genome mapping data in the refined familial spastic paraplegia interval on chromosome 14q.

Autosomal dominant familial spastic paraplegia (AD-FSP) is a genetically heterogeneous neurodegenerative disorder characterized by progressive spasticity of the lower limbs. Three loci on chromosome 14q (SPG3), 2p (SPG4), and 15q (SPG6) were shown to be responsible for AD-FSP. Analysis of recombination events in three SPG3-linked families allowed us to narrow the critical interval from 9 to 5 cM. An approximately 5-Mb YAC contig comprising 32 clones and 90 STSs was built from D14S301 to D14S991, encompassing this region of 14q21. Fifty-six ESTs assigned previously to this region with radiation hybrid (RH) panels Genebridge 4 and G3 were precisely localized on the YAC contig. The 90 STSs positioned on the contig were tested on the TNG RH panel to compare our YAC-based map with an RH map at a high level of resolution. Comparison between our map and the whole genome mapping data on this interval of chromosome 14q is discussed.

Chromosome Mapping↗
PubMed1998

Novel muscle chloride channel (CLCN1) mutations in myotonia congenita with various modes of inheritance including incomplete dominance and penetrance.

Autosomal-dominant and -recessive myotonia congenita are caused by mutations in the skeletal muscle voltage-gated chloride channel gene (CLCN1). We searched for mutations in this gene in 20 unrelated families with myotonia congenita. We identified 11 different mutations in 10 families. Two of five new mutations (Ala313Thr and Ile556Asn) were both autosomal recessive and dominant with either reduced penetrance or incomplete dominance. Mutations in the CLCN1 gene do not therefore necessarily behave in a classic Mendelian manner.

Adult↗
PubMed1998

A systematic study of oligodendrocyte growth factors as candidates for genetic susceptibility to MS. French Multiple Sclerosis Genetics Group.

OBJECTIVE: To test 23 genes coding for growth factors and their receptors as candidates for MS genetic susceptibility in 84 multiplex families of French origin by linkage analysis. BACKGROUND: Epidemiologic studies have indicated that genetic susceptibility in MS exists. To identify MS susceptibility genes, association and linkage studies were performed with candidate genes suggested by the pathology of MS. The most consistent result was genetic association and linkage of MS to human leukocyte antigen (HLA) DR15. Recent advances in the knowledge of MS pathology have suggested that the oligodendrocyte, the myelin-forming cell in the CNS, and its growth factors might play a crucial role in MS. METHODS: Fifty-two polymorphic markers within or flanking 23 candidate genes were used. Data were analyzed with the maximum likelihood score (MLS) approach. We also searched for a genetic interaction with HLA. RESULTS: Negative results were obtained for all candidate genes. The lower limits of the relative risk (Xs) possibly excluded for any candidate gene ranged from 1.3 to 2.8. Positive MLS values (up to 0.93) were observed for transforming growth factor beta 3 (TGFbeta3) in HLA DR15-associated families, suggesting a possible role for this growth factor in interaction with HLA. CONCLUSIONS: Oligodendrocyte growth factors do not play a significant role in MS genetic susceptibility, at least in the tested sample. TGFbeta3, the only gene highlighted by this study, deserves further analysis.

Adult↗
PubMed1998

[Acute post-traumatic aortic insufficiency: transesophageal echocardiography in the diagnosis and therapy of the lesions].

A 58-year-old car driver suffered a road accident responsible for severe blunt thoraco-abdominal trauma. Transoephageal echocardiography, performed following the secondary development of a diastolic murmur, confirmed the presence of aortic incompetence due to commissural avulsion and guided the surgical treatment, which consisted of commissural suspension under cardiopulmonary bypass via a mini transverse trans-sternal incision. The rarity of acute aortic valve incompetence following non-penetrating thoracic trauma is illustrated by the data of the literature. This lesion is due to either avulsion of a sigmoid cusp or commissure, or laceration of the valvular tissue. Transthoracic echocardiography confirms the reality of aortic incompetence suggested clinically by appearance of a diastolic murmur, but confirmation of the mechanism of the lesions is based on transoesophageal echocardiography which allows perfectly safe and rapid visualization of the mechanism of the valvular lesion, investigation of associated lesions and guidance of therapeutic management.

Accidents, Traffic↗
PubMed1998

[Genetic susceptibility to multiple sclerosis (MS). INSERM Network of Clinical Research on the Genetic Susceptibility to MS].

The clinical manifestations and neuropathological signs of Multiple Sclerosis (MS) have been known for more than a century, but the cause of MS remains unknown. Epidemiological studies indicate that MS is a multi-factorial disease implicating both environmental factors and genetic susceptibility. The role of HLA in the genetic susceptibility to MS has been known since the seventies. Advances in human genetics now allow a systematic approach to genetic susceptibility in MS: possible strategies are reviewed.

Genetic Predisposition to Disease↗