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Biomedical subjects

W Camu

Publications and source records attributed to W Camu.

45 records · Page 3Linked to original sources
PubMed1993

Fasting plasma and CSF amino acid levels in amyotrophic lateral sclerosis: a subtype analysis.

Data from the literature about plasma and CSF amino acid (AA) levels in amyotrophic lateral sclerosis (ALS) remain controversial. To refine such analyses we used HPLC, and report a study of plasma and CSF AA concentrations in patients with ALS, the type of the disease (spinal and bulbar onset) being precisely determined. In ALS, there is a decrease in the plasma levels of the large neutral amino acids (LNAA) alanine, isoleucine, leucine, methionine and tyrosine which was particularly striking in the bulbar type (p < 0.05). Plasma glutamate levels do not differ between ALS and controls, but are significantly increased in ALS with spinal onset and decreased in the bulbar type (p < 0.05 vs controls, p < 0.001 bulbar vs spinal). In CSF, the analysis of the whole ALS group shows no difference from controls. However, there is an increase of CSF serine, glutamine and alanine in ALS with spinal onset (p < 0.05). Our results do not support an abnormal profile of excitatory AA concentrations in ALS. The heterogeneous changes we observed, mainly concerning LNAAs, may be explained by a blood-CSF barrier disturbance in the disease. As AA levels clearly differ between ALS types, with low concentrations in bulbar ALS, this dual profile probably explains some of the discrepancies between previous studies.

Amino Acids↗
PubMed1993

Embryonic wing and leg motoneurons have intrinsically different survival properties.

Although spinal motoneurons in the chick embryo are born in a rostro-caudal gradient, the timing of their naturally occurring cell death varies in the opposite sense: brachial motoneurons (MNs) die later than lumbar MNs. We used in vitro methods to determine whether this difference results from factors intrinsic or extrinsic to the MNs. Embryonic MNs were purified from E5 lumbar and brachial spinal cord by a method that enriches for MNs with heightened trophic requirements; they were cultured in serum-free medium. In the absence of muscle extract, death of both populations was rapid; similar results are obtained in ovo after limb ablation. In the presence of muscle extracts, however, lumbar MNs always died more rapidly than brachial MNs, as in the normal embryo. We tested the ability of wing and leg bud extracts to provide trophic factors for MNs in culture. MNs from a given level responded equally well to wing or leg extracts. However, dose-response studies showed that near-maximal survival of brachial MNs was obtained with lower concentrations of limb extract than those required for optimal survival of lumbar MNs. These results suggest that the delayed apoptosis in the brachial MN population is not a result of differing peripheral trophic support, but is intrinsically programmed, at least partially through a higher sensitivity to trophic factors.

Animals↗
PubMed1993

Maturation and integration of purified foetal neurons transplanted into the adult brain.

Fetal neural transplants presently developed as a therapeutic strategy for neurodegenerative diseases include both the neurons of interest and their cellular environment. These glial and vascular cells may be detrimental by, for instance, expressing foreign MHC antigens. This study was undertaken to determine whether purified neurons would survive transplantation into an adult host brain. Embryonic rat spinal neurons were purified by panning and transplanted into adult hosts' brain. During the first three weeks post-transplantation the grafts contained essentially packed immature neurons. Later transplants contained large, multipolar neurons, demonstrating the ability of transplanted neurons to mature in the adult environment. The adult host appears actively involved in the integration of such a transplant by complementing it with microglial and vascular cells.

Animals↗
PubMed1993

[Growth and survival factors of spinal motoneurons].

The development of motoneurons in the spinal cord is strongly dependent on their interactions with their target tissue, skeletal muscle, and with other cells of the central nervous system. The molecular nature of these interactions has remained obscure for many years. However, over the last few years, known growth factors have been shown to have biological activity on the survival of motoneurons, at least in culture. The factors that have been studied are members of the FGF family (fibroblast growth factors), the TGF-beta family (transforming growth factor-beta), CNTF (ciliary neurotrophic factor) and CDF-LIF (cholinergic development factor-leukaemia inhibitory factor). There are also strong reasons to suppose that at least one member of the neurotrophin family (the family that contains Nerve Growth Factor) is involved in motoneuron development. A more detailed analysis of the biological role of each of these factors should not only enlighten us as to the importance of cell-cell interactions in development of the motoneuron, but also open the way to attempts to slow motoneuron death in pathological situations, either in animals or in man.

Animals↗
PubMed1992

Purification of embryonic rat motoneurons by panning on a monoclonal antibody to the low-affinity NGF receptor.

Available methods for purifying motoneurons to homogeneity from rodent spinal cord involve retrograde labelling and fluorescence-activated cell sorting, making them costly and time consuming. Motoneurons are the only neurons within the 15-day embryonic rat spinal cord to express the p75 low-affinity NGF receptor and we show that monoclonal antibody 192-IgG, which binds to the extracellular domain of p75, selectively labels a sub-population of large multipolar ventral spinal cord neurons in vitro. We have developed a bench-top panning method for purifying these motoneurons using antibody 192-IgG. Approximately 10(5) cells/spinal cord are obtained in 2 h by this method; 95% of them express p75 in culture. They rapidly put out neurites on laminin substrata, and their survival is enhanced by extracts of skeletal muscle. Using the panning method in conjunction with centrifugation on a 6.8% metrizamide cushion, separate populations of large and small motoneurons were obtained, each containing more than 90% neurons staining with antibody 192. The large motoneurons had choline acetyltransferase activities/cell approximately 4-fold greater than those of dissociated total spinal cells and 7-fold higher than those of the small motoneurons. These methods should be of considerable use for studies on factors affecting motoneuron survival and development and for transplantation of highly purified neuronal populations.

Animals↗
PubMed1990

Transplantation of serotonergic neurons into the 5,7-DHT-lesioned rat olfactory bulb restores the parameters of kindling.

In order to restore a normal pattern of kindling, kindled rats, previously lesioned in the olfactory nuclei with 5,7-dihydroxytryptamine, were grafted with serotonin (5-HT) neurons in the right olfactory bulb and then implanted for kindling procedure. It was observed that complete 5-HT lesions accelerated the kindling profile, and that the transplants containing 5-HT neurons restored, in lesioned rats, quite normal parameters.

5,7-Dihydroxytryptamine↗
PubMedDate not supplied

Motoneuron survival factors: biological roles and therapeutic potential.

The existence of factors that promote motoneuron survival in the spinal cord at critical stages of development was first deduced 50 yr ago. The large amount of work that has been put into characterizing such factors reflects both their biological importance and the hope that such molecules may be used therapeutically to slow motoneuron death in pathologies such as the spinal muscular atrophies and amyotrophic lateral sclerosis. Since 1990, several factors have been shown to have in vitro and/or in vivo activities that suggest they play a role in regulating motoneuron survival. Their physiological functions during motoneuron development are probably different and complementary. Several of them seem reasonable candidates for preclinical development, but many crucial experiments remain to be done.

Amyotrophic Lateral Sclerosis↗
PubMedDate not supplied

[Adverse efects of riluzole (Rilutek) in the treatment of amyotrophic lateral sclerosis].

Amyotrophic lateral sclerosis (ALS) is a rapidly fatal degenerative disorder of the motoneurones which was without any effective therapy until 1997. Riluzole (Rilutek) has been the first patented drug used in its specific treatment. In order to evaluate the tolerability profile of this molecule, a Pharmacovigilance study was undertaken in the Department of Neurology B at the Montpellier University Hospital. A total of 153 patients were studied and all observed side-effects were listed in the French bank of Pharmacovigilance. Riluzole induced one or more adverse effects in 50.3 per cent of patients. The most frequent were gastrointestinal disturbances, hepatotoxicity and asthenia. Dermatological, haematological, neuropsychiatric and metabolic side-effects were also reported. This study shows an acceptable safety profile for riluzole. Due to its mode of action, riluzole could potentially be used in the treatment of other neurodegenerative diseases involving glutamate excitotoxicity. Subsequently, Pharmacovigilance will have to be carried out to establish the proper use of riluzole.

Aged↗