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Biomedical subjects

J Reboul

Publications and source records attributed to J Reboul.

At least 19 recordsLinked to original sources
PubMed2000

Cytokines in genetic susceptibility to multiple sclerosis: a candidate gene approach. French Multiple Sclerosis Genetics Group.

The immune system is involved in the pathophysiology of multiple sclerosis (MS) but the initiating antigen(s) is not yet identified. Since cytokines control both the intensity and the quality of the immune response they may be relevant candidates for the genetic susceptibility to MS. To analyze the contribution of type 1 and type 2 cytokine and cytokine receptor genes in the genetic susceptibility to MS, we have examined, in 116 French MS sibpairs, whether there is significant linkage between MS and 15 cytokine or cytokine receptor genes using 31 highly polymorphic genetic markers. The data were analyzed using the maximum likelihood score and the transmission disequilibrium approaches. None of the candidate genes tested was significantly linked to MS on the whole population. However, after stratification of the analysis on the basis of sharing (or not) of the HLA-DRB1*1501 allele, indication of linkage was found for the IL2-RB gene. These findings suggest that the IL2-RB locus contributes to the genetic susceptibility in a subgroup of MS patients.

Cytokines↗
PubMed1999

Familial factors influence disability in MS multiplex families. French Multiple Sclerosis Genetics Group.

BACKGROUND: Both genetic and environmental factors play a role in the pathophysiology of MS and may influence the clinical expression of the disease. OBJECTIVE: To determine the contribution of familial factors to the clinical expression of MS. METHODS: The French Multiple Sclerosis Genetics Group identified 87 sibling pairs. For each patient, sex, age at onset, duration of the disease, and disease course from onset were recorded. Disability was determined by the progression index (PI), defined as the ratio of the Expanded Disability Status Scale (EDSS) score disease duration when the latter exceeded 5 years. Statistical analyses were performed either with a group of patients (clinical features, relation between human leukocyte antigen and clinical features) or with a group of sibpairs (concordance for clinical features). RESULTS: The mean age at onset was 29.6 years, the ratio of women to men was 59:28, and the mean PI was 0.27. There was no correlation for disease course and age at onset between sibs with MS. In contrast, we observed a weak but significant correlation of the PI in MS sibpairs (r = 0.234, p = 0.03). CONCLUSION: This study revealed a concordance in MS sibling pairs for the disease severity, supporting the hypothesis that the degree of disability might be partly influenced by familial factors (environmental or genetic).

Adult↗
PubMed1999

The type I interferon receptor: structure, function, and evolution of a family business.

Recent results indicate that coherent models of how multiple interferons (IFN) are recognized and signal selectively through a common receptor are now feasible. A proposal is made that the IFN receptor, with its subunits IFNAR-1 and IFNAR-2, presents two separate ligand binding sites, and this double structure is both necessary and sufficient to ensure that the different IFN are recognized and can act selectively. The key feature is the duplication of the extracellular domain of the IFNAR-1 subunit and the configurational geometry that this imposes on the intracellular domains of the receptor subunits and their associated tyrosine kinases.

Amino Acid Sequence↗
PubMed1999

Comparative genomic analysis of the interferon/interleukin-10 receptor gene cluster.

Interferons and interleukin-10 are involved in key aspects of the host defence mechanisms. Human chromosome 21 harbors the interferon/interleukin-10 receptor gene cluster linked to the GART gene. This cluster includes both components of the interferon alpha/beta-receptor (IFNAR1 and IFNAR2) and the second components of the interferon gamma-receptor (IFNGR2) and of the IL-10 receptor (IL10R2). We report here the complete gene content of this GART-cytokine receptor gene cluster and the use of comparative genomic analysis to identify chicken IFNAR1, IFNAR2, and IL10R2. We show that the large-scale structure of this locus is conserved in human and chicken but not in the pufferfish Fugu rubripes. This establishes that the receptor components of these host defense mechanisms were fixed in an ancestor of the amniotes. The extraordinary diversification of the interferon ligand family during the evolution of birds and mammals has therefore occurred in the context of a fixed receptor structure.

Amino Acid Sequence↗
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↗
PubMed1995

Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit generated by alternative processing of a new member of a cytokine receptor gene cluster.

The cellular receptor for the alpha/beta interferons contains at least two components that interact with interferon. The ifnar1 component is well characterized and a putative ifnar2 cDNA has recently been identified. We have cloned the gene for ifnar2 and show that it produces four different transcripts encoding three different polypeptides that are generated by exon skipping, alternative splicing and differential use of polyadenylation sites. One polypeptide is likely to be secreted and two are transmembrane proteins with identical extracellular and transmembrane domains but divergent cytoplasmic tails of 67 and 251 amino acids. A mutant cell line U5A, completely defective in IFN-alpha beta binding and response, has been isolated and characterized. Expression in U5A cells of the polypeptide with the long cytoplasmic domain reconstitutes a functional receptor that restores normal interferon binding, activation of the JAK/STAT signal transduction pathway, interferon-inducible gene expression and antiviral response. The IFNAR2 gene maps at 0.5 kb from the CRFB4 gene, establishing that together IFNAR2, CRFB4, IFNAR1 and AF1 form a cluster of class II cytokine receptor genes on human chromosome 21.

Alternative Splicing↗
PubMed1995

Exclusion of the candidate locus FSP1 in six families with late-onset autosomal dominant spastic paraplegia.

Hereditary spastic paraplegias are neurological hereditary conditions of unknown aetiology. In pure spastic paraplegia, most of the pedigrees display an autosomal dominant mode of inheritance. A gene for pure autosomal dominant spastic paraplegia (ADSP), termed FSP1, was mapped to chromosome 14q in a large pedigree with early-onset disease. This locus was tested by linkage analysis in six large French kindreds of ADSP with late-onset disease, using four microsatellites spanning a 9 cM interval including FSP1. FSP1 could be excluded in five of the six families, while no evidence for linkage was found in the remaining family. These results suggest that FSP1 is not involved in late onset ADSP, at least in the six families studied.

Adolescent↗
PubMed1994

Genetic heterogeneity in hypokalemic periodic paralysis (hypoPP).

Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder belonging to a group of muscle diseases known to involve an abnormal function of ion channels. The latter includes hypokalemic and hyperkalemic periodic paralyses, and non-dystrophic myotonias. We recently showed genetic linkage of hypoPP to loci on chromosome 1q31-32, co-localized with the DHP-sensitive calcium channel CACNL1A3. We propose to term this locus hypoPP-1. Using extended haplotypes with new markers located on chromosome 1q31-32, we now report the detailed mapping of hypoPP-1 within a 7 cM interval. Two recombinants between hypoPP-1 and the flanking markers D1S413 and D1S510 should help to reduce further the hypoPP-1 interval. We used this new information to demonstrate that a large family of French origin displaying hypoPP is not genetically linked to hypoPP-1. We excluded genetic linkage over the entire hypoPP-1 interval showing for the first time genetic heterogeneity in hypoPP.

Adolescent↗
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

Mutations in the muscle sodium channel gene (SCN4A) in 13 French families with hyperkalemic periodic paralysis and paramyotonia congenita: phenotype to genotype correlations and demonstration of the predominance of two mutations.

Hyperkalemic periodic paralysis (hyperPP), paramyotonia congenita (PC) and PC with myotonia permanens are closely related muscle disorders of genetic origin due to allelic mutations in the muscle sodium channel gene, SCN4A. Seven families of French origin with hyperPP were studied. Five of these had the Thr704Met mutation, but 2 families, genetically linked to SCN4A, failed to show any of the known mutations of SCN4A. Correlations between the phenotype and the genotype were made for patients with the Thr704Met mutation. All 12 patients over 30 years old with the Thr704Met mutation presented muscle weakness due to degeneration of muscle fibers in addition to periodic paralysis. Only approximately 12.5% of patients with the Thr704Met mutation presented with clinical myotonia and about 50% with hyperkalemia. One family with PC displayed the Gly1306Val mutation with a phenotype similar to the one already reported for this mutation. Five families with either PC or PC with myotonia permanens had the Thr1313Met mutation indicating that the severity of myotonia and its permanence were variable. Two mutations of SCN4A were found to be predominant in these 13 families: the Thr704Met and the Thr1313Met mutations. Only 2 families with the Thr704Met mutation and 3 families with the Thr1313Met shared the same SCN4A haplotype determined with intragenic dinucleotide repeats. Recurrent mutations of SCN4A may contribute to the predominance of these two mutations in the French population.

Adolescent↗
PubMed1993

[Peroperative use of Cell Saver in elective surgery on the abdominal aorta].

In order to determine the impact of intraoperative autotransfusion on vascular surgical care, data related to 200 abdominal aortic surgical operations performed over a 20 months period were prospectively analysed. Volumes of blood salvaged and transfused during and after each operation were considered. One hundred and twenty one patients had an intraoperative autologous transfusion at a mean volume of 616 +/- 410 ml. Among them, 36 patients (43%) had only their own autotransfused blood and no other homologous blood components were required. Rapid autotransfusion was associated neither with significant haemolysis, nor with coagulopathy. Neither mortality nor morbidity was related to intraoperative autotransfusion. These data suggest that intraoperative autotransfusion is a safe replacement method in major vascular surgery. The procedure should be used in conjunction with preoperative donations when feasible.

Aged↗
PubMed1993

Intrathecal synthesis of beta 2-microglobulin and lysozyme: differential markers of nervous system involvement in patients infected with human immunodeficiency virus type 1.

beta 2-Microglobulin and lysozyme were determined in paired serum and cerebrospinal fluid samples from 137 patients, using immunofluorometry and ELISA, respectively. Of these patients, 54 were infected by human immunodeficiency virus type 1 (HIV1) (including 20 AIDS dementia patients), 73 were HIV1-seronegative with neurological diseases (meningitis (n = 10), multiple sclerosis (n = 29), other neurological diseases (n = 34)) and 10 were controls. Intrathecal synthesis of beta 2-microglobulin occurred in each group. Conversely, lysozyme intrathecal synthesis was found only in meningitis (10/10) and in HIV1-infection (24/54). A pathological increase in beta 2-microglobulin intrathecal synthesis (> or = 2 mg/l) was observed in 45 patients (34 HIV1-infected patients and 11 HIV1-seronegative patients with neurological diseases). Serum concentration and intrathecal synthesis of beta 2-microglobulin were correlated only in the 20 AIDS dementia patients. The cerebrospinal fluid beta 2-microglobulin and lysozyme concentrations were correlated in the 54 HIV1-infected patients only. Blood CD4 + T-cell count was correlated negatively with beta 2-microglobulin intrathecal synthesis but not with lysozyme intrathecal synthesis. These data suggest that in the absence of any central nervous system opportunistic process the increase of beta 2-microglobulin intrathecal synthesis (> or = 2 mg/l) may be a reliable marker of central nervous system involvement in HIV1-infected patients. Intrathecal synthesis of lysozyme was related principally to HIV1-encephalitis and central nervous system opportunistic processes.

AIDS Dementia Complex↗
PubMed1992

Intrathecal synthesis of proteins: from immunoglobulins to prealbumin.

The assessment of proteins intrathecal synthesis (ITS) is an essential step in the CSF analysis. It can be established qualitatively by different ratios and quantitatively by empirical formulae. Schuller and Sagar's formula was proposed 10 years ago for the calculation of IgG ITS. From this calculation, the antibody specific activity of intrathecal immunoglobulins may be also evaluated. The same principle may be used for complement components and for different other CSF proteins. Two examples (concerning Fibronectin and prealbumin ITS) demonstrate the usefulness of this approach, which can be programmed by a computer.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Descending thoracic aorta as an inflow source for late occlusive failures following aortoiliac reconstruction.

From November 1984 to March 1990, 10 descending thoracic aorta-to-femoral artery bypass procedures were performed after failure of one or several aortoiliofemoral reconstructions. All patients were men, mean age 60 years. Indications included noninfected false aneurysm of an infrarenal end-to-side aortoprosthetic anastomosis in one case; one occlusion of an axillofemoral bypass; degradation of an aortobifemoral prosthetic graft; two occlusions of aortofemoral bypass; and five occlusions of aortobiliac or aortobifemoral bypasses. Eight bifurcated grafts, one aortoprosthetic tube graft, and one aortopopliteal tube graft were inserted. One patient died 23 days postoperatively of multiple organ failure. Three patients underwent a successful seconary lower limb reconstruction procedure (prosthetic limb thrombectomy, embolectomy, femoral bifurcation angioplasty in one case each). Mean survival time was 14 months (range 3-48 months). Two patients were lost to follow-up, and one died of myocardial infarction six months postoperatively with a patent bypass. Graft thrombosis occurred in two patients. One was treated by thrombectomy at five months, the other was treated by in-situ thrombolysis at 15 months. Both of these patients had patent grafts at 12 and 21 months, respectively. The four other patients had patent grafts at 48 months. Primary patency was 55.5% (5/9 survivors) and secondary patency was 100% (9/9). This is a relatively simple method for constructing an extraanatomic aortofemoral or aortobifemoral bypass in late failures of aortoiliofemoral reconstructive surgery without having to re-enter the abdomen.

Aged↗