Prospect for a 60 GHz multicharged ECR ion source.

The conceptual design of a fourth generation hybrid electron cyclotron resonance (ECR) ion source operated at 60 GHz is proposed. The axial magnetic mirror is generated with a set of three NbSn coils, while the hexapole is made with room temperature (RT) copper coils. The motivations for such a hybrid development are to study further the ECR plasma physics and the intense multicharged ion beams' production and transport at a time when a superconducting (SC) hexapole appears unrealistic at 60 GHz.

Chromosomes 4 and 13 in beta-carboline-induced seizures in mice: benzodiazepine binding.

Methyl beta-carboline-3-carboxylate (beta-CCM) is a ligand for the benzodiazepine (BZD) binding site of the GABA-A receptors with convulsive properties. We provided evidence for the involvement of a fragment of mouse chromosomes 4 and 13 in beta-CCM-induced seizures in a previous paper. Here, we analyzed, through [3H]-flumazenil binding, whether central BZD binding sites could be involved in the physiological processes underlying these differences of genetic sensitivities.

Whole blood serotonin and plasma beta-endorphin in autistic probands and their first-degree relatives.

Background: Whole blood serotonin (5-HT) and C-terminally directed beta-endorphin protein immunoreactivity (C-ter-beta-EP-ir) are known to be elevated in autistic subjects and might be possible markers of genetic liability to autism. This study thus investigates the familial aggregation of 5-HT and of C-ter-beta-EP-ir levels in first degree relatives of autistic probands.

Methods: In a sample of 62 autistic subjects and 122 of their first-degree relatives, compared to age and sex-matched controls, we measured 5-HT by radioenzymology and C-ter-beta-EP-ir by radioimmunoassay.

Genetic factors regulate processes related to anxiety in mice.

The propensity for anxiety-related behavior has been studied by comparing two highly inbred strains of mice, ABP/Le and C57BL/6ByJ, in two behavioral procedures, open-field and light-dark preference. Their Mendelian F2 population allowed us to evaluate the putative involvement of four easily identifiable loci in anxiogenic processes. In fact, chromosomal regions containing the brown, pink-eyed dilution and short-ear loci on the 4th, 7th and 9th chromosomes respectively are associated with anxiety-related behavior patterns.

Convulsive effects of a benzodiazepine receptor inverse agonist: are they related to anxiogenic processes?

The linkage-testing strain of ABP/Le mice carries six mutations which express in easily identifiable phenotypes. By crossing this strain with a traditional inbred strain (C57BL/6ByJ) which is the 'wild type' for the mutated ABP/Le loci, we produced Mendelian populations, intercrosses and backcrosses so as to estimate whether the sensitivity to methyl beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine receptor inverse agonist, and anxiety-related behaviour could be related to a common genetically determined substrate. We have shown that one locus on chromosome 9 is associated with beta-CCM-induced seizures and three loci on chromosomes 4, 7 and 9 are associated with anxiogenic processes.

A mouse mutant strain highly resistant to methyl beta-carboline-3-carboxylate-induced seizures.

The convulsant properties of methyl beta-carboline-3-carboxylate (beta-CCM) were evaluated in the TaT-fm/GncTa+/+Tfm strain carrying the tabby coat color (Ta) and/or the testicular feminization (Tfm) gene. When injected intraperitoneally within a 5-60 mg/kg dose range, beta-CCM-induced convulsions in less than 25% of the mice, thus providing evidence for a high resistance of this strain, as compared to classical strains of mice. However, this strain responds normally to the convulsant pentylenetetrazol (PTZ), suggesting a specific resistance to beta-CCM.

Ras involvement in signal transduction by the serotonin 5-HT2B receptor.

The family of serotonin 5-HT2 receptors stimulates the phospholipase C second messenger pathway via the alpha subunit of the Gq GTP-binding protein. Here, we show that agonist stimulation of the 5-HT2B receptor subtype stably expressed in the mouse fibroblast LMTK- cell line causes a rapid and transient activation of the proto-oncogene product p21ras as measured by an increase in GTP-bound Ras in response to serotonin. Furthermore, 5-HT2B receptor stimulation activates p42mapk/p44mapk (ERK2/ERK1) mitogen-activated protein kinases as assayed by phosphorylation of myelin basic protein.

Low-dose naltrexone effects on plasma chemistries and clinical symptoms in autism: a double-blind, placebo-controlled study.

The effect of month-long naltrexone (NTX) treatment at a daily oral dose of 0.5 mg/kg/day was contrasted with placebo (PLC) in a double-blind study with conjoint clinical and biochemical evaluations of therapeutic effects. Modest clinical benefits were achieved with both PLC and NTX, with marginally better overall results following NTX, and degree of improvement appeared to be related to plasma chemical profiles.

Difference between plasma N- and C-terminally directed beta-endorphin immunoreactivity in infantile autism.

Objective: The authors investigated whether there is excessive opioid activity in infantile autism by measuring plasma beta-endorphin in patients with autism compared with patients who had Rett's syndrome and normal comparison subjects.

Methods: Radioimmunoassays for beta-endorphin using C-terminally and N-terminally directed antisera were applied to plasma samples from 67 children who met both DSM-III-R and ICD-10 diagnostic criteria for infantile autism, 22 girls with Rett's syndrome, and 67 normal children matched in age and sex with the children with autism.

Results: Median N-terminally directed beta-endorphin immunoreactivity appeared to be slightly lower in subjects with autism (7 pg/ml) and clearly higher in the girls with Rett's syndrome (40 pg/ml) than in the comparison subjects (9 pg/ml).

Serotonin receptors and therapeutics.

Since its discovery, serotonin (5-hydroxytryptamine = 5-HT) has become a major player on the neurotransmitter "stage". Multiple receptor subtypes for 5-HT have been identified and classified, and a vast pharmacology of 5-HT has emerged. In particular, 5-HT has been shown to exert marked effects on the cardiovascular system, central nervous system (CNS) and gastrointestinal (GI) tract, and important ligands have been developed that mimic or block its action selectively.

Increase of human platelet serotonin uptake by atypical histamine receptors.

Histamine and the guanosine 3',5'-cyclic monophosphate (cGMP)-inducing agent sodium nitroprusside both increased serotonin (5-HT) uptake and cGMP levels in isolated human platelets in vitro. Histaminergic stimulation was observed at concentrations ranging from 10 nM to 0.25 microM [mean effective concentration (EC50) = 0.

Metabolism of 6-fluoro-DL-tryptophan and its specific effects on the rat brain serotoninergic pathway.

We administered 6-fluoro-DL-tryptophan (6F-Trp) to rats (50-200 mg/kg i.p.) and evaluated its neurochemical effects on central catechole and indole compounds; we also determined the time course of its action, together with its metabolism and kinetics in four rat brain areas.

[Opiate hypothesis in infantile autism? Therapeutic trials with naltrexone].

The opioid hypothesis suggests that childhood autism may result from excessive brain opioid activity during neonatal period which may constitutionally inhibit social motivation, yielding autistic isolation and aloofness (Panksepp, 1979). This hypothesis has now received strong support and is currently based on three types of arguments: (1) similarity between autistic symptomatology and abnormal behaviors induced in young animals by injections of exogenous opioids, such as increasing social aloofness and decreasing social vocalization; (2) direct biochemical evidence of abnormalities of peripheral endogenous opioids being reported in autism and (3) therapeutic effects of the long lasting opioid receptor blocking agent naltrexone in autism. In this article, we give description of open and double-blind studies of naltrexone in autism.

Genetic difference in sensitivity to beta-carboline: evidence for the involvement of brain benzodiazepine receptors.

The convulsive effects of methyl beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine receptor ligand, are different in two inbred strains of mice: BALB/cBy mice are more sensitive to beta-CCM than C57BL/6J mice. In the present article, we report the effects of [3H]flunitrazepam binding in these two strains, which suggest a possible explanation of the differences in their sensitivity to beta-CCM by the involvement of brain benzodiazepine receptors.

Biochemical and pharmacological characterization of histamine-mediated up-regulation of human platelet serotonin uptake. Evidence for a subclass of histamine H2 receptors (H2h) highly sensitive to H2 receptor antagonists.

The stimulatory effect of histamine: H (1.2 to 3-fold increase) on serotonin (5-HT) uptake by human platelets was observed after a 5 min incubation period in the presence of 2.5 X 10(-7) M histamine, followed by subsequent 5 min incubation of the platelets with 10(-7) M [3H] 5-HT.