ABSTRACT
Palmitoyl-lysophosphatidylcholine promotes a transient calcium influx in lymphoma cells. Previously, it was observed that this influx was accompanied by a temporary increase in propidium iodide permeability that appeared linked to calcium entry. Those studies demonstrated that cobalt or nickel could block the response to lysophosphatidylcholine and raised the question of whether the calcium conductance involved specific channels. This communication describes a series of experiments to address that issue. The time dependence and structural specificity of the responses to lysophosphatidylcholine reinforced the hypothesis of a specific channel or transporter. Nevertheless, observations using patch clamp or calcium channel blockers suggested that this "channel" does not involve proteins. Alternative protein-mediated mechanisms such as indirect involvement of the sodium-calcium exchanger and the sodium-potassium ATPase were also excluded. Experiments with extracellular and intracellular calcium chelators suggested a common route of entry for calcium and propidium iodide. More directly, the ability of lysophosphatidylcholine to produce cobalt-sensitive permeability to propidium iodide was reproduced in protein-free artificial membranes. Finally, the transient nature of the calcium time course was rationalized quantitatively by the kinetics of lysophosphatidylcholine metabolism. These results suggest that physiological concentrations of lysophosphatidylcholine can directly produce membrane pores that mimic some of the properties of specific protein channels.
Subject(s)
Calcium Channels/physiology , Calcium/metabolism , Lysophosphatidylcholines/pharmacology , Animals , Calcium Channels/drug effects , Cell Membrane Permeability , Cobalt/metabolism , Ion Transport , Lymphoma , Mice , Nickel/metabolism , Patch-Clamp Techniques , Spectrometry, Fluorescence , Tumor Cells, CulturedSubject(s)
Electroencephalography , Epilepsy, Temporal Lobe/physiopathology , Adolescent , Adult , Brain/physiopathology , Child , Humans , Models, Anatomic , Scalp , Skull , Tomography, X-Ray ComputedABSTRACT
As part of our studies on localization of epileptic foci, dipole analysis using averaged spikes were compared with that using individual spikes for 25 patients with localization related epilepsy. Our results are as follows. 1) In the group which showed stable dipoles from individual spikes, dipole localization from averaged and individual spikes were similar, although the former showed a higher dipolarity and more stable location, for the entire spike discharge including the peak, trough and wave. The high dipolarity was due to improved signal to noise ratio obtained from averaging. 2) The cases with centrotemporal spike focus including benign childhood epilepsy with centrotemporal spikes showed more reliable dipoles. In the cases with frontal lobe epilepsy, reliable dipoles were rarely obtained even with averaged spikes. Each method provided independent information, so they are of complementary value.
Subject(s)
Electroencephalography/statistics & numerical data , Epilepsies, Partial/physiopathology , Adolescent , Adult , Child , Child, Preschool , Epilepsy, Frontal Lobe/physiopathology , HumansABSTRACT
Forty-six children with refractory epilepsy (12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 20 with undetermined epilepsy) were treated by high-dose (serum level above 100 micrograms/ml) valproate (VPA) therapy. Monotherapy was used with 34 patients and two drugs with 12. Serum VPA concentrations ranged from 105.1 to 198.4 micrograms/ml. Assessment of initial response to treatment, after the serum level had reached the appropriate level, showed seizures to be completely controlled in 15 (32.6%) of 46 patients and improved in 12 (26.1%) (50% or more). Follow-up of more than 6 months after the time of initial response showed control of seizures in 14 (30.4%) and improvement in 11 (23.9%). The initial effect on EEG was the disappearance of epileptic discharges in 3 (6.5%) of 46 patients and marked improvement in 15 (32.6%). Follow-up revealed the disappearance of epileptic discharges in 7 (15.2%) and marked improvement in 9 patients (19.6%). High-dose VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike-waves during slow-wave sleep. Control of atypical absences and myoclonic seizures was relatively good. Hypofibrinogenemia and thrombocytopenia were sometimes encountered but these side effects were reversible with reduction of dosage.
Subject(s)
Epilepsy/drug therapy , Valproic Acid/therapeutic use , Adolescent , Anticonvulsants/therapeutic use , Child , Child, Preschool , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Electroencephalography/drug effects , Epilepsies, Partial/drug therapy , Epilepsy, Generalized/drug therapy , Female , Follow-Up Studies , Humans , Infant , Male , Spasms, Infantile/drug therapy , Valproic Acid/blood , Valproic Acid/pharmacologyABSTRACT
A long-term follow-up study of 89 patients of Lennox-Gastaut syndrome (LGS) disclosed the persistent occurrence of seizures in 68 patients (76.4%) and severe mental defect in 48 (53.9%). An analysis of the correlation between the mental and seizure prognoses confirmed that the persistence of minor seizures could result in mental deterioration. An examination of the evolutional changes in EEG demonstrated that diffuse slow spike-waves characteristic of LGS gradually disappeared, while focal epileptic discharges, especially multifocal spikes, appeared in spite of the persistence of minor seizures. The diagnostic criteria were satisfied in only 31 (47.0%) of 66 patients with the persistence of minor seizures. Patients with multiple independent spike foci and minor seizures were considered to belong to a specific type of epilepsy, namely the severe epilepsy with multiple independent spike foci (the severe epilepsy with MISF). The seizure and mental prognoses were poorer in patients who evolved into the severe epilepsy with MISF than others.
