Differential role for the striatum and cerebellum in response to novel movements using a motor learning paradigm.

The aim of this pilot study was to examine the role of the striatum and cerebellum in the adaptation to a novel movement within a sequence of practiced movements using a motor learning paradigm. The performance of patients in the early or advanced stages of Parkinson's disease (PD) and of patients with damage to the cerebellum (CE) was compared, respectively to a group of aged and young matched controls on an adapted version of the Mirror-Tracing Test. In this task, subjects were required to trace a series of complex figures in two conditions: (1) a Practiced condition, in which the figures were composed of the juxtaposition of three simple designs that were extensively practiced before; and (2) a Mixed condition in which triads were created by replacing the last simple figure of the triads in the Practiced condition by a new simple figure that had never been traced individually before. Results showed that all clinical groups were slower than controls at tracing the Practiced triads. Most interestingly, however, only patients in the advanced stages of PD showed increased completion time to trace the triads in the Mixed condition. This suggests that a bilateral striatal dysfunction affects the ability to adapt to a novel motion within a sequence of practiced movements. Although exploratory, these results support a functional dissociation between the striatum and cerebellum in acquiring visuomotor skilled behaviors.     

Cadmium treatment and lead-induced suppression of splenic erythropoiesis.

Young adult female mice were injected with lead acetate (d 0). Following injection, determinations were made of the percentages of radioactive iron (59Fe) uptake into the hemoglobin of erythrocytes produced by spleen. Control 59Fe uptake percentage vacillated between 4.2 and 5.5 within the 7-d period of observation. On d 4 following lead treatment, splenic percentages were dramatically reduced below those of the saline-injected controls; by d 6 the splenic 59Fe uptake of lead-treated mice was comparable to that of controls. For rodents injected with cadmium chloride on 0, the 59Fe uptake values showed a statistically significant elevation by d 2, which was extended beyond that of the controls' d 4 value. For those animals receiving both lead and cadmium (d 0), the uptake percentages paralleled those of the controls throughout the 7-d period of observation. These data suggest that the inhibitory effect of lead on erythropoiesis of the spleen is blocked by a concurrent cadmium treatment. Results are interpreted in regard to a possible vulnerable target and competition for the target by lead and cadmium.     

Contribution of Calcium Channel Subtypes to the Intracellular Calcium Signal in Sensory Neurons: The Effect of Injury

Background: Although the activation-induced intracellular Ca2+ signal is disrupted by sensory neuron injury, the contribution of specific Ca2+ channel subtypes is unknown.

Methods: Transients in dissociated rat dorsal root ganglion neurons were recorded using fura-2 microfluorometry. Neurons from control rats and from neuropathic animals after spinal nerve ligation were activated either by elevated bath K+ or by field stimulation. Transients were compared before and after application of selective blockers of voltage-activated Ca2+ channel subtypes.

Results: Transient amplitude and area were decreased by blockade of the L-type channel, particularly during sustained K+ stimulation. Significant contributions to the Ca2+ transient are attributable to the N-, P/Q-, and R-type channels, especially in small neurons. Results for T-type blockade varied widely between cells. After injury, transients lost sensitivity to N-type and R-type blockers in axotomized small neurons, whereas adjacent small neurons showed decreased responses to blockers of R-type channels. Axotomized large neurons were less sensitive to blockade of N- and P/Q-type channels. After injury, neurons adjacent to axotomy show decreased sensitivity of K+-induced transients to L-type blockade but increased sensitivity during field stimulation.     

Long-term survival in an infant with urethral atresia

Complete urethral atresia is an anomaly that previously was incompatible with life. We report on a surviving infant with this anomaly. As a fetus urinary decompression was accomplished with a vesicoamniotic shunt. Peritoneal dialysis was initiated shortly after birth and at 9 months supramembranous scrotal inlay urethroplasty was performed to provide for egress of urine from the bladder. A maternal renal allograft was performed when he was 12 months old. When the patient was 3 1/2 years old he had normal renal function and emptied the bladder to completion through the reconstructed urethra. Although mildly delayed, he continues to progress with all developmental milestones.     

Neuropathy associated with “benign” anti-myelin-associated glycoprotein IgM gammopathy: Clinical,immunological, neurophysiological pathological findings and response to treatment in 33 cases

We studied 33 patients presenting with a peripheral neuropathy associated with non-malignant anti-myelin-associated glycoprotein (MAG) IgM monoclonal gammopathy (MG) in an attempt to delineate their clinical, immunological, electrophysiological and pathological characteristics; we also reviewed our experience concerning long-term follow-up and therapy. Peripheral neuropathy associated with non-malignant anti-MAG IgM MG was observed mostly in males (sex ratio 7.2), and mean age at onset was 67 years (range 46–81). A predominantly sensory pattern was noted in more than 80% of cases, although some patients were affected by a predominantly motor peripheral neuropathy. Although disease progression was slow in most cases, 45% of patients suffered severe disability, and in 2 cases, the patient's death appeared to stem directly from the neuropathy. The electrophysiological findings were indicative of a demyelinating process in 90% of cases, and electron microscopic examination of nerve biopsy specimens demonstrated widening of the myelin lamellae in more than 95% of cases. Most of our patients showed a disappointing response to steroids and chemotherapy or plasma exchanges. Intravenous immune globulin, evaluated in 17 patients, had a transient, mostly subjective effect in 35% and led to a clear-cut improvement in 24% of cases. We did not observe any correlation between the severity of the clinical picture and the anti-sulphoglucuronyl paragloboside antibody titre; in individual cases, clinical improvement occurred without lowering of IgM levels. Although the severity and the rate of progression may greatly vary from patient to patient, the combination of clinical, electrophysiological and pathological features delineates a characteristic pattern in peripheral neuropathy associated with non-malignant anti-MAG IgM MG.     

The effects of a competitive NMDA receptor antagonist (CGS-19755) on cerebral blood flow and pH in focal ischemia.

We report the effects of intravenous infusion of CGS-19755, a potent competitive N-methyl-D-aspartate (NMDA) antagonist, on local cerebral pH (LCpH) and local CBF (LCBF) in rats with occluded left middle cerebral and common carotid arteries. LCpH and LCBF were determined simultaneously by a double-label autoradiographic technique 4 h after vascular occlusion in three groups: no treatment, carrier infused, and a group receiving CGS-19755 at 10 mg/kg bolus immediately after occlusion followed by infusion at 5 mg kg-1 h-1 for 4 h. Compared with rats receiving carrier, several cortical structures on the side of occlusions showed significantly higher CBF in rats receiving CGS-19755. This drug also corrected the pH in several left cortical structures to values significantly higher than in the rats receiving carrier. The correction in LCpH was not limited to those regions showing significant elevations in LCBF. In the nonoccluded hemisphere, CGS-19755 significantly increased the hemispheric mean blood flow from 122 +/- 17 to 221 +/- 64 ml 100 g-1 min-1 (mean +/- SD of all structures, p less than 0.01) without any changes in LCpH. Cortical but not basal ganglia infarct volume was significantly smaller in rats receiving CGS-19755 than in the carrier-treated group. These results suggest that, at least partially, the neuroprotective effect of CGS-19755 in ischemia may be related to changes in CBF and pH in addition to its antagonist effect on the NMDA receptor.     

Purification of B16-F1 melanoma autocrine motility factor and its receptor.

Tumor autocrine motility factor (AMF) is a cytokine which stimulates both random and directed cell migration by self-producing cells. AMF has been detected in and purified from serum-free conditioned medium of murine B16-F1 melanoma cells. Under nonreducing conditions AMF migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band of Mr 55,000, whereas under reducing conditions it migrates as a single polypeptide of Mr 64,000. Two-dimensional polyacrylamide gel electrophoresis of the purified AMF resolved two polypeptides with isoelectric points of 6.35 (major) and 6.4 (minor). No carbohydrate side chains were detected in the B16-F1 AMF. Purified AMF stimulated B16-F1 cell migration in a dose-dependent fashion and bound directly in a protein-protein-binding assay to the AMF receptor, a cell surface glycoprotein of Mr 78,000 [glycoprotein (gp) 78]. The involvement of gp78 in AMF-stimulated function was demonstrated by motility assays. These results suggest that AMF is the natural ligand for the gp78-AMF receptor.     

Autosomal dominant centronuclear myopathy]

In a family 6 members in 3 generations were affected by centronuclear myopathy (CNM) of autosomal dominant inheritance. The apparent onset was in the early forties and the disease progressed slowly. Limb weakness was predominant. Strabismus was present in 5 cases and calves hypertrophy in 3. Serum creatinine kinase was always within the normal range. In one case myotonic bursts were found at electromyography. In 2 cases brain stem auditory evoked potential studies demonstrated abnormal prolongation of interpeak latencies I-III and favoured subclinical nervous system involvement. Muscular biopsies showed typical features of centronuclear myopathy with 50 to 80% central nuclei. In two cases immunocytochemical labelling of dystrophin showed staining in the sarcoplasm in favour of an arrest in the morphogenesis of developing myofiber. Others families with autosomal dominant CNM in the literature and also some sporadic adult cases had similar clinical features.