Role of the glycine site of the N-methyl-D-aspartate receptor in synaptic plasticity induced by pairing

In the hippocampal CA1 region of the rat, activity-dependent plasticity requires substantial postsynaptic depolarization and activation of the N-methyl-D-aspartate glutamate receptor subtype (NMDAR). Exogenous and endogenous compounds selectively modulate NMDAR function by acting at the glycine coagonist site. Here we investigate the modulatory role of the glycine site in the induction of bidirectional synaptic plasticity. Plasticity was induced by pairing low-frequency afferent pulses with different levels of postsynaptic depolarization in the absence and presence of glycine site compounds. We found strong dependence of glycine site agonist modulation on membrane voltage during induction. Thus, D-serine and glycine were more effective in enhancing long-term potentiation (LTP) during pairing of small depolarization (-60 or -50 mV) with subthreshold EPSCs than during pairing of stronger depolarization (-40 mV) with suprathreshold synaptic responses. The glycine site role in bidirectional synaptic plasticity was studied with the selective antagonist 7-chlorokynurenic acid. Blockade of the glycine site during the pairing reversed the direction of plasticity from LTP towards long-term depression. The magnitude of depression was dependent on antagonist concentration and the level of depolarization during the pairing. Thus, these experiments demonstrate the role of the glycine site in the induction of bidirectional synaptic plasticity.     

Histological analysis of the location of effective thalamic stimulation for tremor. Case report

Chronic electrical stimulation of the thalamus is an effective treatment for essential and parkinsonian tremor. Although the preferred surgical target is generally accepted to lie within the ventral intermediate nucleus (Vim), the relationship between the surgically defined target and the true histologically defined target is addressed in only a few reports, due in large measure to the need for advanced cytoarchitectonic techniques to define the borders of the thalamic nuclei. The authors report on a patient who underwent effective thalamic deep brain stimulation (DBS) for tremor. By defining the boundaries of the thalamic nuclei, they were able to relate effective DBS to electrode location within the anterior region of the ventral posterior lateral nucleus--the proprioceptive shell of the sensory nucleus--and the posteroventral region of the ventral lateral nucleus, which are equivalent to the Vim defined by Hassler, et al.     

Primary cardiac Burkitt lymphoma in a child

Primary cardiac lymphoma (PCL) is a rare and usually fatal malignancy, seldom reported in children. This report describes the case of a 10-year-old boy who presented with multiple intracardiac masses which, when biopsied, proved to be small non-cleaved cell (Burkitt's) lymphoma. The first two cycles of chemotherapy according to the LMB 96 protocol were given under close cardiological supervision, with good response. The treatment was then continued with full-dose chemotherapy, without any cardiological complication. The patient who was treated by chemotherapy alone remains in complete remission 36 months after the end of treatment and can presently be considered as cured, without late cardiac effect.     

Development and validation of a scale for rating motor compensations used for reaching in patients with hemiparesis: the reaching performance scale

BACKGROUND AND PURPOSE: Recent movement analysis studies have described compensatory movement strategies used by people with hemiparesis secondary to stroke during reaching and grasping tasks. The purpose of this article is to describe the development of a new scale--the Reaching Performance Scale (RPS)--for assessing compensatory movements for upper-extremity reaching in people with hemiparesis secondary to stroke. SUBJECTS: Twenty-eight individuals with hemiparesis, with a mean age of 54.9 years (SD=18.6), participated. METHODS: The study design involved scale development with expert panels and criterion standards for validity. Participants were evaluated on the new scale as well as other clinical tests for validity. They were videotaped while performing reaching and grasping movements. RESULTS: The RPS scores correlated with measurements of grip force and Chedoke-McMaster Stroke Assessment and Upper Extremity Performance Test for the Elderly (TEMPA) scores. The RPS discriminated patients with different impairment levels according to the Chedoke-McMaster Stroke Assessment. Preliminary intrarater and interrater reliability coefficients were acceptable for the whole scale. Mean kappa values on individual scale components for 3 raters represented a mean of 67% (SD=13.5%) agreement. DISCUSSION AND CONCLUSION: Although the RPS shows some types of validity, more rigorous tests of reliability are needed for meaningful conclusions. This study is a first step in validating the scale to assess efficacy of intervention for motor recovery of the arm.     

Rapidly progressive dementia due to Mycobacterium neoaurum meningoencephalitis

Dementia developed in a patient with widespread neurologic manifestations; she died within 5 months. Pathologic findings showed granulomatous inflammation with caseation necrosis, foreign body-type giant cells, and proliferative endarteritis with vascular occlusions. Broad-range polymerase chain reaction identified Mycobacterium neoaurum as the possible pathogen. Central nervous system infection by M. neoaurum may result in rapidly progressive dementia.     

Ribozyme-based gene-inactivation systems require a fine comprehension of their substrate specificities; the case of delta ribozyme

The ability of ribozymes (i.e. RNA enzymes) to specifically recognize and subsequently catalyze the cleavage of an RNA substrate makes them attractive for the development of therapeutic tools for the inactivation of both viral RNAs and mRNAs associated with various diseases. Several applicable ribozyme models have been tested both in vitro and in a cellular environment, and have shown significant promise. However, several hurdles remain to be surpassed before we generate a useful gene-inactivation system based on a ribozyme. Among the most important requirements for further progress are a better understanding of the features that contribute to defining the substrate specificity for cleavage by a ribozyme, and the identification of the potential cleavage sites in a given target RNA. The goal of this review is to illustrate the importance of both of these factors at the RNA level in the development of any type of ribozyme based gene-therapy. This is achieved by reviewing the recent progress in both the structure-function relationships and the development of a gene-inactivation system of a model ribozyme, specifically delta ribozyme.