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Biomedical subjects

B Fontaine

Publications and source records attributed to B Fontaine.

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

[Pure cerebellar syndrome associated with anti-Hu antibodies].

Anti-Yo is the most frequent antibody associated with pure paraneoplastic cerebellar degeneration. Cerebellar degeneration may be associated with anti-Hu antibody but other signs of nervous system involvement occur during the course of the disease. We report the case of a 69-year old man presenting with a severe acute cerebellar dysfunction of sudden onset. High titers of anti-Hu antibodies were detected in serum and cerebrospinal fluid by immunohistochemistry and western blot. No other neurological symptom was found after a follow-up of 18 months. Biopsy of a mediastinal lymph node revealed a poorly differentiated carcinoma. We suggest that the course of the anti-Hu syndrome may rarely be similar to the anti-Yo syndrome.

Aged↗
PubMed1995

Altered calcium currents in human hypokalemic periodic paralysis myotubes expressing mutant L-type calcium channels.

In a genome-wide search, linkage of hypokalemic periodic paralysis (HypoPP), a muscle disease with autosomal dominant inheritance, to chromosome 1q31-32 and cosegregation with the gene encoding the L-type calcium channel/DHP receptor alpha 1 subunit has been reported (Fontaine et al., 1994). Here we show the extended haplotypes of a large HypoPP family who made the detection of the gene product possible. Sequencing of cDNA synthesized from RNA isolated from muscle specimens of two affected family members revealed a G-to-A transition of nucleotide 3716. This base exchange predicts a substitution of histidine for arginine 1239 located in segment IVS4 of the channel protein. By restriction fragment analysis, the mutation was detected in the genomic DNA of all affected family members. Myotubes cultured from the muscle specimens also revealed the mutation suggesting the expression of mutant L-type calcium channel/DHP receptors. Whole-cell recordings of 20 such myotubes showed a strong reduction of the DHP sensitive, slowly activating and inactivating L-type current density to 30% of the current in normal controls. A rapidly activating and inactivating current component (third-type), which is distinct from the also occurring T-type current, was increased. We conclude that HypoPP is a disease of the skeletal muscle DHP receptor. The point mutation in repeat IV of the protein may have a similar effect as drugs which downregulate the channel activity by binding to this domain.

Calcium Channels↗
PubMed1994

Genes with triplet repeats: a new class of mutations causing neurological diseases.

Microsatellites, simple tamdem repeats of 2 to 4 nucleotide sequences, are widely distributed throughout the genome. Trinucleotide repeats are found every 300 to 500 kb. Recently, a new type of mutation was described involving a specific expansion of triplets within or in close proximity to a gene. Expanded triplets have been found in the genes causing six different neurological disorders: fragile X syndrome (FRAXA), spinal and bulbar muscular atrophy (SBMA), myotonic dystrophy (DM), Huntington's disease (HD), spinocerebellar ataxia type 1 (SCA1), and dentato-rubra-pallidoluysian atrophy (DRPLA). These neurological disorders have in common a variable age of onset and clinical severity, as well as a decrease in the age of onset over generations, known as anticipation. These unusual characteristics are related to the observation that expanded repeats are unstable both in meioses and mitoses. A younger age of onset and an increase in severity correlate with a higher number of repeats. Interestingly, particular haplotypes are in disequilibrium with the mutation for FRAXA, DM and HD, suggesting instability for selected chromosomes. How expanded triplets affect the expression and the function of genes is still unknown. Since neurodegenerative disorders are often variable in age of onset and clinical severity, the list of expanding triplet mutations should increase in the very near future.

DNA↗
PubMed1994

Mapping of the hypokalaemic periodic paralysis (HypoPP) locus to chromosome 1q31-32 in three European families.

Hypokalaemic periodic paralysis (HypoPP) is an autosomal dominant muscle disease thought to arise from an abnormal function of ion channels. Performing a genome-wide search using polymorphic dinucleotide repeats, we have localized the HypoPP locus in three families of different geographic origin to chromosome 1q31-32, by linkage analysis. Using an intragenic microsatellite, we also demonstrate that the gene encoding the muscle DHP-sensitive calcium channel alpha 1 subunit (CACNL1A3) maps to the same region, sharing a 5 centiMorgan (cM) interval with the HypoPP locus. Moreover, CACNL1A3 co-segregates with HypoPP without recombinants in the two informative families, and is therefore a good candidate for the HypoPP gene.

Calcium Channels↗
PubMed1994

Linkage of a new locus for autosomal dominant familial spastic paraplegia to chromosome 2p.

Autosomal dominant familial spastic paraplegia (AD-FSP) is a genetically heterogeneous neurodegenerative disorder characterized by a spasticity of the lower limbs. A locus causing AD-FSP (FSP1) has been previously mapped to chromosome 14q. We now report linkage of a second AD-FSP locus (FSP2) to chromosome 2p21-p24 in five of seven French families and one large Dutch pedigree. The analysis of recombination events and multipoint linkage place FSP2 within a 4 cM interval flanked by loci D2S400 and D2S367.

Adolescent↗
PubMed1994

Dementia in two histologically confirmed cases of multiple sclerosis: one case with isolated dementia and one case associated with psychiatric symptoms.

During the past 10 years, considerable attention has been devoted to cognitive impairment in multiple sclerosis. Occasionally this impairment may be so severe that multiple sclerosis presents as a dementia associated with only minor neurological signs and symptoms. The cases of two women affected by multiple sclerosis who presented with a pure dementia are reported. In the first patient, a progressive apragmatic behavioural disturbance with reduced short term memory and learning abilities were the main clinical features. Neuropathological examination of the brain disclosed numerous plaques in the periventricular white matter, with severe atrophy of the corpus callosum. Plaques were also seen in the white matter of both hippocampus and in the columns of the fornix. The impairment of short term memory could be linked to these lesions. Behavioural changes were probably related to the bilateral lesions of the long associative bundles that disconnected the frontal lobes from other parts of the cerebral hemispheres. In the second patient, visual hallucinations were associated with cognitive dysfunction. MRI showed large plaques in the white matter of both left frontal and temporal lobes. Smaller plaques were also present in the periventricular white matter of the occipital lobes, the nature of which were confirmed by a stereotactic biopsy.

Adult↗
PubMed1994

Alphabetical paragraphia in a limited middle cerebral artery stroke.

A Yugoslavian perfectly bilingual for French and Serb had a limited left middle cerebral artery stroke. He developed a peculiar dysgraphia characterised by the use of Latin characters (French spelling) to transcribe Serb phonemes that would normally have been spelt in the Cyrillic alphabet. This dysgraphia was likely to be due to an impairment of the allographic procedure. It is concluded that allographs of the two alphabets are produced concomitantly in bialphabetical patients during the allographic procedure.

Agraphia↗
PubMed1994

The phenotype of "pure" autosomal dominant spastic paraplegia.

We studied 23 families with "pure" autosomal dominant spastic paraplegia. Examination of 142 at-risk individuals allowed identification of 70 patients, including 12 who were clinically affected but unaware of symptoms. The frequency of lower limb muscle weakness, decreased vibration sense, hyperreflexia in the upper limbs, and sphincter disturbances increased with the disease duration. The distribution of age at onset was unimodal, with a mean onset of 29 years (range, 1 to 68). The clinical manifestations of "early-onset" (< 29 years) and "late-onset" (> 29 years) patients were not significantly different. Age at onset varied as much within families as among families; anticipation and imprinting did not occur. No clinical criteria allowed differentiation among the families studied. Only linkage studies can provide accurate classification of this disease.

Adult↗
PubMed1993

A set of STS assays targeting the chromosome 22 physical framework markers.

The widespread use of the sequence-tagged site (STS) as a quick, efficient, and reproducible assay for comparing physical and genetic map information promises to facilitate greatly long-range goals of the mapping of the human genome. We have designed 21 STS assays for loci on human chromosome 22. These assays primarily tag the physical framework markers of the long arm of 22, but additional assays have been designed from known genes and loci in the neurofibromatosis 2 (NF2) region. The availability of these assays will make these loci available to the research community without physical transfer of materials and will serve as start points for further efforts to physically map chromosome 22 with yeast artificial chromosome clones.

Animals↗
PubMed1993

Periodic paralysis, myotonia congenita and sarcolemmal ion channels: a success of the candidate gene approach.

The classification of periodic paralyses and myotonic syndromes has been a subject of debates for the last 40 yr. Recent advances in molecular biology have led geneticists to reconsider this old question, using a candidate gene approach. Two groups of disorders have now emerged: (1) muscle sodium channel-associated diseases which include hyperkalemic periodic paralysis and its clinical variants, as well as paramyotonia congenita; (2) muscle chloride channel-associated disorders which comprise both the dominant and recessive form of myotonia congenita. This review is focussed on these recent discoveries.

Genotype↗
PubMed1993

Phase II multicenter study of epirubicin for hormone-resistant prostatic cancer with measurable soft tissue disease.

Twenty-six patients with prostatic cancer were treated with courses of epirubicin at 3-week intervals, starting at an initial intravenous dose of 75 mg/m2. All patients had progressive disease after orchiectomy and/or antiandrogen therapy and had measurable soft tissue lesions. There were three partial responders (response rate: 12%; 95% confidence limits: 4-29%). Major toxicity was myelosuppression, and there were two drug-related deaths. Epirubicin in this dose and schedule cannot be recommended for treatment of prostatic cancer.

Aged↗
PubMed1993

Elevation of serum phosphate affects parathyroid hormone levels in only 50% of hemodialysis patients, which is unrelated to changes in serum calcium.

Hyperphosphatemia is said to cause hyperparathyroidism either by depressing the plasma levels of ionized calcium and/or by affecting serum 1,25(OH)2 vitamin D3 levels. Direct evidence that hyperphosphatemia contributes to hyperparathyroidism in hemodialysis patients is unclear because previous published data are with older parathyroid hormone (PTH) assays. Phosphate was added to the dialysate of 15 patients for 12 wk whose predialysis serum phosphates were between 1.5 and 1.9 mM (4.7 to 5.9 mg/dL) in order to further increase their serum phosphate by 0.75 mM (2.4 mg/dL) without adjustments in other medications. No patient was on vitamin D therapy. In half of the patients, PTH levels remained unchanged (nonresponders; 214 +/- 64 versus 219 +/- 60 ng/L), whereas in the other patients, PTH rose from 204 +/- 53 to 338 +/- 60 ng/L (P < 0.05; responders). The degree of induced hyperphosphatemia was virtually identical in both groups, 1.7 mM increasing to 2.4 mM. Ionized calcium was unchanged in both groups after phosphate. Plasma 1,25(OH)2 vitamin D3 levels were low to start with and remained low throughout. Nonresponders had been on dialysis twice as long as responders and had consumed over seven times more aluminum salts. Nonresponders had higher postdeferoxamine increments in plasma aluminum (3,588 +/- 1,466 versus 603 +/- 390; P < 0.05), although neither these amounts nor plasma levels were in the toxic range.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1993

[Symptomatic heterozygotic adrenoleukodystrophy in adults. 10 cases].

Adult adrenoleukodystrophy is a X-linked peroxisomal disease associated with the accumulation of very long chain fatty acids (VLCFA) in tissues and body fluids. The diagnosis is established on the demonstration of elevated VLCFA in blood and cultured skin fibroblasts. Women are affected in nearly 15% of cases and neurological symptoms and/or signs develop in 53% of them. Identifying these women is important because of genetic counseling and a possible therapeutic approach. Ten cases of symptomatic heterozygous adult adrenoleukodystrophy are reported. Mean age at the time of diagnosis was 44.6 +/- 9.3 years. All patients presented with spastic paraparesis with inconstant and mild sensory or bladder disturbances. Cognitive impairment was present in 1 case. Cerebrospinal fluid was normal. Adrenal function in response to tetracosactide injection was abnormal in 1/7 cases. Electromyography detected a peripheral neuropathy in 1 case. Somatosensory evoked responses were abnormal in all cases, visual and auditory evoked responses in respectively 3/6 cases and 3/4 cases. Brain MRI detected non specific abnormalities in 3/7 cases; spinal cord MRI was normal in 3/3 cases. The familial history was helpful for the diagnosis in 3/10 cases. Examination of pedigrees detected 5 hemizygous and 1 asymptomatic heterozygous cases. All the patients were enrolled in a dietary study which adret with low VLCFA is currently under evaluation.

Adrenoleukodystrophy↗