Central benzodiazepine receptors in human brain: estimation of regional Bmax and KD values with positron emission tomography.

Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.     

Linear relationship between the maintenance of hippocampal long-term potentiation and retention of an associative memory.

The hypothesis that the maintenance or decay of an associative memory trace after an extended retention interval is a function of the residual strength of the synapses originally strengthened during learning was examined in a classical conditioning paradigm in which high-frequency stimulation of a hippocampal input--the medial perforant path--served as a conditioned stimulus. Rats received perforant path stimulus-foot shock pairings while engaged in a previously acquired food-motivated lever-pressing task. Conditioned suppression of lever pressing was the behavioral measure of learning and retention of the association. Stimulus trains to the perforant path at an intensity above the threshold for eliciting a population spike induced long-term potentiation of synaptic transmission in the dentate gyrus. Synaptic potentials recorded extracellularly in the dentate gyrus were subsequently monitored for 31 days to examine quantitatively the decay of synaptic potentiation, a period after which retention of the learned association was assessed. All rats learned the association to a similar extent and displayed equivalent amounts of long-term potentiation by the end of conditioning. A slowly decaying function of synaptic potentiation was observed in remembering rats, i.e., rats with high retention performance after the 31-day learning-to-retention interval, while forgetting was associated with a rapid decay of long-term potentiation. Behavioral performance at the long-term memory test was linearly correlated with the amplitude of long-term potentiation maintained just prior to the retention test. The results favor the hypothesis that long-term associative memory depends, at least in part, on the maintenance of elevated synaptic strengths in the pathway activated during learning and suggest a role for the lasting component of long-term potentiation in the maintenance of memory.     

The prognostic value of evoked responses from primary somatosensory and auditory cortex in comatose patients.

OBJECTIVE: To evaluate somatosensory and auditory primary cortices using somatosensory evoked potentials (SEPs) and middle latency auditory evoked potentials (MLAEPs) in the prognosis of return to consciousness in comatose patients. METHODS: SEPs and MLAEPs were recorded in 131 severe comatose patients. Latencies and amplitudes were measured. Coma had been caused by transient cardiac arrest (n=49), traumatic brain injury (n=22), stroke (n=45), complications of neurosurgery (n=12) and encephalitis (n=3). One month after the onset of coma patients were classified as awake, still comatose or dead. Three months after (M3), they were classified into one of the 5 categories of the Glasgow outcome scale (GOS). RESULTS: At M3, 41.2% were dead, 47.3% were conscious (GOS 3-5) and 11.5% had not recovered consciousness. None of the patients in whom somatosensory N20 and auditory Pa were absent did return to consciousness and in the post-anoxic group, reduced cortical amplitude too was always associated with bad outcome. Conversely, N20 and Pa were present, respectively, in 33/69 and 34/69 patients who did not recover. CONCLUSIONS: The prognostic value of SEPs and MLAEPs in comatose patients depends on the cause of coma. Measurement of response amplitudes is informative. Abolition of cortical SEPs and/or cortical MLAEPs precludes post-anoxic comatose patients from returning to consciousness (100% specificity). In any case, the presence of short latency cortical somatosensory or auditory components is not a guarantee for return to consciousness. Late components should then be recorded.     

Purification and characterization of a kinase specific for the serine- and arginine-rich pre-mRNA splicing factors.

Members of the SR family of pre-mRNA splicing factors are phosphoproteins that share a phosphoepitope specifically recognized by monoclonal antibody (mAb) 104. Recent studies have indicated that phosphorylation may regulate the activity and the intracellular localization of these splicing factors. Here, we report the purification and kinetic properties of SR protein kinase 1 (SRPK1), a kinase specific for SR family members. We demonstrate that the kinase specifically recognizes the SR domain, which contains serine/arginine repeats. Previous studies have shown that dephosphorylated SR proteins did not react with mAb 104 and migrated faster in SDS gels than SR proteins from mammalian cells. We show that SRPK1 restores both mobility and mAB 104 reactivity to a SR protein SF2/ASF (splicing factor 2/alternative splicing factor) produced in bacteria, suggesting that SRPK1 is responsible for the generation of the mAb 104-specific phosphoepitope in vivo. Finally, we have correlated the effects of mutagenesis in the SR domain of SF2/ASF on splicing with those on phosphorylation of the protein by SRPK1, suggesting that phosphorylation of SR proteins is required for splicing.     

La prothèse totale du coude GUEPAR

Résumé Un grand nombre de prothèses du coude sont actuellement disponibles, beaucoup de critères les opposent les unes aux autres. Après les premières prothèses à charnière contrainte, les prothèses semicontraintes et plus récemment les prothèses à glissement se sont imposées. La prothèse à glissement GUEPAR se situe dans l'évolution récente des implants du coude. Nous rapportons ici les résultats des trente-neuf premières arthroplasties réalisées au sein du Guepar de 1986 à 1991, sur 33 coudes rhumato?des, 4 destructions post-traumatiques, 1 spondylarthrite ankylosante et 1 arthrose sur chondrocalcinose.

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The Guepar total elbow arthroplasty

Summary The Guepar total elbow replacement is a low friction, minimally constrained gliding prosthesis. The humeral and ulnar components are of metal with intramedullary stems, which are cemented. There is a sigmoid shaped, high density polyethylene interposition bearing. The authors have used the prosthesis in 33 patients with rheumatoid arthritis, 4 with post-traumatic problems, one with chondrocalcinosis and another with degenerative changes of uncertain aetiology. In the patients with rheumatoid arthritis, one sustaine a posterior dislocation and two suffered deep infection. In the remaining 30, the overall results were good at an average review of 32 months. The mean range of movement had increased by 31° and pain was absent in 28 elbows. In the management of rheumatoid arthritis total elbow arthroplasty must be part of an overall plan of treatment. Severe involvement of the wrist and shoulder must be dealt with before elbow replacement is considered.

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Nous remercions Mr J. H. Aubriot, M. Condamine, A Deburge, B Lassale, T Le Balc'h, J. Y. Nordin et J Witvoet, membres du GUEPAR (Groupe pour l'utilisation et l'étude des prothèses articulaires) de nous avoir donné leurs observations     

Differential effect of cyclosporin A (CyA) on IgE response: role of CyA-induced suppressor cells

Administration of cyclosporin A (CyA, 30 mg/kg) for the five days following immunization of Brown Norway rats with DNP14-OVA in alum abolished the primary total and specific IgE response, whereas this treatment had no significant effect on the secondary IgE response. On the contrary, with a single injection of CyA on the day of priming, the secondary IgE response only is abolished. The inhibition of the secondary IgE response could be attributed to the induction by a single dose of CyA of nylon wool-adherent spleen cells, as shown by passive transfer experiments. CyA might thus affect the IgE response variously depending on single or repeated administrations.