Autoradiographic localization of dopamine uptake sites in the rat brain with3H-GBR 12935

Summary The firing rate and terminal excitability of identified nigrostriatal dopamine (DA) neurons was determined before, and over a 10–15 min period following, direct intrastriatal administration of the glutamate (GLU) agonist NMDA, or saline. NMDA (0.025 and 0.075 mol) produced a short latency increase in DA cell firing rate. In 7/8 cases, this increase in firing rate was accompanied by a profound reduction in terminal excitability. The decrease in excitability usually outlasted the increase in firing rate (sometimes by more than 8 min), and was superseded at a later stage by a marked increase in excitability. None of these effects were seen with saline (n=5), and they could all be blocked by preadministration of the competitive NMDA antagonist AP-7 (0.025 mol; n=6). The sequence of events leading to the observed results is argued to be as follows; NMDA initially excites striatal efferents to the DA cell, which through disinhibition and direct stimulation increase DA cell firing rate. Increased firing rate leads to enhanced striatal DA release. Dopamine's inhibitory influence pre-empts any effect NMDA itself may have on the terminals of nigrostriatal neurons, and counteracts NMDA's stimulatory effect on striatal output cells. Furthermore, the marked reduction in terminal excitability suggests that DA becomes the dominant influence in the striatum for a time. Hence, the net outcome of the injection is augmented striatal DA tone. Later, the effect of residual NMDA becomes predominant once more.     

FISH characterization of a supernumerary r(1)(::cen→q22::q22→sq21::) chromosome associated with multiple anomalies and bilateral cataracts

We describe the case of a 15‐year‐old girl with multiple congenital anomalies, dysmorphic features, severe kyphoscoliosis, growth and mental retardation, and the absence of speech, in whom 35% of the cells carried a supernumerary ring chromosome 1. Fluorescence in situ hybridization (FISH) analysis using YAC/BAC clones spanning the region from 1p13 to 1q21 made it possible to determine the genomic content and structure of the ring(1), which was found to consist of the cytogenetic bands 1q21–22. A complex structure was delineated in the ring chromosome with a partial inverted duplication delimited by markers WI‐7732 and WI‐607, with WI‐7396 and WI‐8386 being the boundaries of the single copy segment. Comparison of the clinical signs of other patients with mosaic r(1) reported in the literature allowed the identification of a patient sharing a number of clinical signs including cataracts. Given that mutations of the GJA8 gene encoding connexin 50 (Cx50) and mapping to 1q21 have been associated with the presence of cataracts, it is possible that a gain in copy number or a rearrangement of GJA8 may contribute to cataractogenesis.     

The treatment of carotid artery bifurcation stenoses with systematic stenting: experience of first 100 consecutive cardiological procedures

Carotid endarterectomy still represents the gold standard treatment of carotid artery bifurcation stenosis but percutaneous angioplasty with stenting is rapidly growing as a non-invasive alternative. In this paper we report the results of systematic application of carotid stenting performed in a cardiological setting, particularly as regards clinical management of patients and technical approach. One-hundred (100) procedures of carotid artery stenting (CAS) on 94 consecutive patients, both symptomatic and asymptomatic, with a carotid stenosis > 70%, were performed over a period of 30 months. The technical approach was directly derived from coronary angioplasty with use of large lumen guiding catheters, 0.014 in. intravascular guidewires and distal protection devices usually employed in coronary interventions. In 3 cases, a post-carotid endarterectomy restenosis and in 97 cases, a de-novo lesion, were treated respectively; in 71 cases, the degree of stenosis was 71-89% and in 29 cases, 90-99%. Cerebral protection was obtained with a distal to the lesion endovascular filter in 63 cases. Immediate technical success, i.e. residual stenosis of the treated vessel < 30% and no significant pathologic acceleration of blood flow (< 1.5 m/sec) at the Doppler ultrasound evaluation, was achieved in all procedures (100%). Ninety-six (96) procedures were totally uncomplicated; in-hospital cerebral complications were 1 TIA, 2 minor and 1 major strokes; at 30-day follow-up one additional major stroke occurred. Despite a particularly high incidence of comorbidities, neither unfavorable cardiological complications nor neurologic deaths were reported. Systematic CAS is a feasible treatment of the carotid artery bifurcation stenosis with high procedural success and low perioperative and short term complications. Its performance in a cardiological setting can combine satisfying procedural results and potentially successful handling of cardiovascular complications.     

Cell-based assays for the detection of MOG antibodies: a comparative study

Journal of Neurology - The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the...     

Regional distribution of the messenger RNA coding for the neuropeptide cholecystokinin in the human brain examined by in situ hybridization

The regional localization of mRNA coding for the neuropeptide cholecystokinin (CCK) has been studied in the human brain by in situ hybridization using a 32P-labelled synthetic oligonucleotide. Autoradiograms were quantified using computer-assisted microdensitometry. Positive hybridizing cells were seen in the neocortex, the claustrum, the hippocampus and the amygdala with the highest densities observed in the claustrum, some cortical layers and the CA2 and CA3 regions of the hippocampus. No significant hybridization signal was observed in the substantia nigra, caudate nucleus, putamen, globus pallidus, nucleus accumbens, thalamus, hypothalamus, medulla oblongata and cerebellum. The topographic distribution of neurons expressing CCK mRNA correlates well with that previously reported by immunocytochemistry or radioimmunoassay in brain areas such as the neocortex, the amygdala and the hippocampus. However, some discrepancies were also found, particularly in the basal ganglia, the midbrain, the thalamus and the hypothalamus. These results show that in situ hybridization with oligonucleotide probes together with a semiquantitative analysis can be used to map the distribution of cells expressing CCK mRNA in human postmortem materials.     

Recurrent chest pain as the presenting manifestation of spinal meningioma

We report the case of a 9-year-old boy with a spinal cord meningioma whose only manifestations were recurrent episodes of chest pain lasting for 2 years. This case shows that spinal cord meningioma should be considered among the possible causative factors of chronic chest pain in childhood. Chest pain, meningioma, spinal tumors     

High frequency stimulation of the subthalamic nucleus increases the extracellular contents of striatal dopamine in normal and partially dopaminergic denervated rats

The subthalamic nucleus (STN) has come under focus in Parkinson disease (PD) because of recent advances in the understanding of the functional organization of the basal ganglia in normal and pathological conditions. Manipulations of the STN have been described to compensate for some imbalance in motor output of the basal ganglia in animal models of PD and have been proposed as a potential therapeutic target in humans. Indeed, high frequency stimulation (HFS) (130 Hz) of the STN has beneficial effects in severe parkinsonian patients but the precise mechanisms underlying these clinical results remain to be elucidated. To date, very little is known concerning the effect of HFS-STN on striatal dopaminergic transmission. Since it has been reported that dopaminergic medication may be reduced in PD patients under HFS-STN, our goal was to study the effect of HFS-STN on striatal dopamine (DA) transmission by using intracerebral microdialysis in normal and partially DA denervated rats. Our results show that HFS STN induces a significant increase of extracellular DA in the striatum of normal and partially DA lesioned rats while striatal extracellular levels of DOPAC were not affected. We conclude that HFS-STN acts directly and/or indirectly on striatal DA levels in control or partially DA lesioned rats.     

Leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiency

Three cases of Leigh disease are described. In all three, symptoms began in the first months of life, with muscle hypotonia, lactic acidosis, and psychomotor delay. The diagnosis was made on the basis of the clinical characteristics, biochemical abnormalities, and typical brain magnetic resonance imaging with symmetric lesions suggesting bilateral necrosis at the level of the basal ganglia and of the midbrain. Cytochrome c oxidase (complex IV of the mitochondrial respiratory chain) deficiency was demonstrated in muscle tissue in all patients and confirmed in skin fibroblasts in patient 3. A genetic heterogeneity was present in these patients since only one had a SURF-1 gene mutation. The clinical, biochemical, and neuroradiologic aspects are discussed. Finally, the finding of facial dysmorphisms in the cytochrome c oxidase deficiency observed in one of the described cases is of extreme interest; to our knowledge, this association has never been reported in the literature.