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F Salachas

Publications and source records attributed to F Salachas.

28 records · Page 2Linked to original sources
PubMed1999

Genetics of familial ALS and consequences for diagnosis. French ALS Research Group.

Familial amyotrophic lateral sclerosis (fALS) is a well-recognised condition that accounts for almost 10% of all cases of ALS. Most cases are now known to be transmitted by an autosomal dominant trait. When fALS is compared clinically to sporadic ALS, 20% of cases manifest atypical features such as pain, paraesthesia or urgency micturition. Moreover, a disease duration of over 10 years, with very slow progression, appears to occur almost exclusively in cases of fALS. Studies of superoxide dismutase (SOD1) mutations in fALS have shown that the disease may be multidegenerative, with oculomotor or cerebellar involvement. Molecular genetics has also demonstrated that not all SOD1 mutations have a dominant influence, and the detailed description of the Scandinavian D90A homozygous mutation is very informative in this regard. Misdiagnosis of fALS can be attributed to one of the following situations: (i) atypical phenotype ALS with a multidegenerative profile; (ii) unusually long lasting ALS with mild motor neuron involvement; (iii) significant clinical heterogeneity between affected family members; (iv) low reliability of family history; (v) existence of an unknown or unexpected mode of transmission; and (vi) other multidegenerative disorders with motor neuron involvement. Pedigrees and fALS cases corresponding to these situations are presented.

Adult↗
PubMed1998

Association between centromeric deletions of the SMN gene and sporadic adult-onset lower motor neuron disease.

The telomeric copy (t) of the survival motor neuron (SMN) gene is homozygously deleted in more than 90% of patients with infantile motor neuron disease (MND). In the general population, no homozygous SMNt deletion has been found, whereas 5% of centromeric SMN (SMNc) deletions can be observed. Although SMNt deletions appear causal for infantile and at least some adult-onset spinal muscular atrophy (SMA) (type IV), the respective role of SMN deletions remains unclear in adult-onset MNDs. We studied SMN gene in three different groups of patients with adult-onset MNDs. In sporadic amyotrophic lateral sclerosis (ALS; n = 177) and familial ALS (n = 66), no SMNt deletion had been found, and the frequency of SMNc deletions was not increased. Conversely, among the 14 patients with sporadic pure lower MND (LMND), we found 2 patients with homozygous SMNt deletions (14%) and 5 patients with homozygous SMNc deletions (36%). These data suggest that (1) SMNt deletions do not account for the major part, if any, of adult-onset LMND cases; and (2) SMNc deletions act as a susceptibility factor for LMNDs in adults. The clinical and genetic heterogeneity of LMND cases, including SMA type IV, are yet to be unexplained. Further studies on large groups of adult-onset LMND patients are warranted to refine its nosology.

Adult↗
PubMed1998

Identification of six novel SOD1 gene mutations in familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the premature death of motor neurons. In approximately 10% of the cases the disease is inherited as autosomal dominant trait (FALS). It has been found that mutations in the Cu/Zn superoxide dismutase gene (SOD1) are responsible for approximately 15% of FALS kindreds. We screened affected individuals from 70 unrelated FALS kindreds and identified 10 mutations, 6 of which are novel. Surprisingly, we have found a mutation in exon 3, which includes most of the active site loop and Zn2+ binding sites, a region where no previous SOD1 mutations have been found. Our data increase the number of different SOD1 mutations causing FALS to 55, a significant fraction of the 154 amino acids of this relatively small protein.

Amino Acid Sequence↗
PubMed1997

Influence of neck muscles on mouth pressure response to cervical magnetic stimulation.

Measurement of mouth pressure (Pm) in response to electrical phrenic nerve stimulation (Es) provides a simple noninvasive means to assess diaphragm function. An even simpler measure would be to use the Pm twitch response (Pm,t) to cervical magnetic stimulation (CMS) rather than to Es. Because CMS coactivates the diaphragm and inspiratory neck muscles (INM), CMS-Pm,t accurately reflects diaphragm function only if the corresponding INM contraction does not produce inspiratory pressures by itself. In patients with recent-onset bilateral diaphragm paralysis, it has been demonstrated that CMS-Pm,t was indeed zero; however, INM hypertrophy could change this situation and lead CMS-Pm,t to overestimate the performance of the diaphragm. To address this issue, we studied nine patients with amyotrophic lateral sclerosis (ALS) who had evidence of diaphragmatic paralysis and compensatory hypertrophy and hyperactivity of inspiratory neck muscles. The response to CMS was described in terms of diaphragm electromyogram (EMG), Pm, and abdominal (AB) and rib cage (RC) motion. No EMG response to CMS could be observed in most cases, and CMS was always associated with AB paradox. Nevertheless, a negative Pm,t swing was recorded with an amplitude of -2.6 +/- 1.0 cm H2O (mean +/- SD). We conclude that inspiratory neck muscle hypertrophy can significantly influence the Pm response to CMS. This should be taken into account when using the CMS-Pm combination in patients with possible chronic diaphragm dysfunction.

Aged↗
PubMed1995

Murine hematopoietic progenitor cells produce IL-6 in response to IgE.

Similarly to interleukin-3 (IL-3), IgE is capable of inducing IL-6 production by murine bone marrow cells (BMC). IgE responder cells do not belong to the mature bone marrow compartment but coenrich with hematopoietic progenitors in the low-density fraction of a discontinuous Ficoll gradient. A significant enhancement of IL-6 production is observed after a 4-hour stimulation, reaching a maximum between 24 and 48 hours and is preceded by increased mRNA expression. The effect of IgE on IL-6 production is not mediated by IL-3 since it is not modified by anti-IL-3 antibodies. Upon a 4-hour exposure to IgE or IL-3, a similar percentage of progenitor-enriched BMC expresses IL-6 mRNA (3.9 and 5.4%, respectively, as determined by in situ hybridization), which is not further increased by a combination of both stimuli. IgE and IL-3 responder cells also cannot be distinguished on the basis of size, internal structure, and rhodamine (Rh) retention. The BMC sorted in the most fluorescent Rhbright subset (approximately 0.2% of total BMC) produce 30- to 40-fold more IL-6 than unfractionated cells and are similarly enriched for CFU-cells (CFU-C). The most primitive cells concentrated in the Rhdull fraction do not express this biological activity. The sorted Rhbright population does not contain mature mast cells/basophils or monocytes, and IL-6 is not produced in response to Fc epsilon RI cross-linkage after presensitization with IgE.

Animals↗
PubMed1994

Aggregated IgE mimic interleukin-3-induced histamine synthesis by murine hematopoietic progenitors.

Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by inducing histamine production. This effect does not result from degranulation of histamine-containing cells, but from histamine synthesis, as assessed by the following findings. (1) The histamine content of freshly isolated bone marrow cells is too low to account for the increase in extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine production in the presence of the specific inhibitor of histidine decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic activity and the mRNA expression of HDC were enhanced in response to IL-3 or IgE. Artificial aggregation or formation of IgE immune complexes augmented ther effect on histamine synthesis, indicating that the aggregated form is responsible for this biologic activity. Yet, it is apparently not mediated by Fc epsilon RI because their cross-linkage by dinitrophenyl bovine serum albumin after presensitization with IgE did not induce histamine production by hematopoietic progenitors. Among other aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a consistent but lower effect, whereas IgM and IgA were completely inactive. The target cells of IL-3 and IgE in terms of histamine synthesis do not belong to mature bone marrow populations, especially mast cells. They copurify with hematopoietic progenitors in the low-density layers of a discontinuous Ficoll gradient where they represent around 5% of the cells, as determined by in situ hybridization. This percentage remained the same, regardless of whether the cells were stimulated by IgE or IL-3 alone or by a combination of both, suggesting a common responder cell. In accordance with this notion, histamine-producing cells could not be distinguished from each other on the basis of density, size and internal structure, or rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect of IgE.

Animals↗
PubMed1990

[Neuroleptic malignant-like syndrome following levodopa withdrawal].

The description of a syndrome similar to the neuroleptic malignant syndrome but occurring after levodopa withdrawal in a parkinsonian patient is reported. The imputation of levodopa withdrawal is analyzed according to the method of assessment of unexpected drug reactions used by the French centers of pharmacovigilance. This case is compared to 8 other published ones.

Aged↗
PubMedDate not supplied

[Tolerance of riluzole in a phase IIIb clinical trial].

Within the framework of an early drug access programme launched in 1995, a multicentre open study was initiated in France in order to assess, inter alia, the safety of riluzole (50 mg twice a day) in a total of 2069 patients from 28 centres. This programme, a phase IIIb study with direct individual benefit, had two main objectives: to enable patients to receive riluzole therapy pending regulatory approval and commercial availability and to provide further data on the safety of riluzole in a broader ALS population. The most frequent adverse events related to riluzole treatment were: asthenia, nausea and elevation of serum transaminase levels. These observations, similar to data derived from previous pivotal clinical trials, confirm that riluzole has a satisfactory tolerability profile.

Aged↗