Disrupted Functional and Structural Connectivity in Angelman Syndrome.

BACKGROUND AND PURPOSE: This work investigated alterations in functional connectivity (FC) and associated structures in patients with Angelman syndrome (AS) by using integrated quantitative imaging analysis and connectivity measures. MATERIALS AND METHODS: We obtained 3T brain MR imaging, including resting-state functional MR imaging, diffusion tensor imaging, and 3D T1-weighted imaging from children with AS (n = 14) and age- and sex-matched controls (n = 28). The brains of patients with AS were analyzed by measuring FC, white matter microstructural analysis, cortical thickness, and brain volumes; these were compared with brains of controls. RESULTS: Interregional FC analysis revealed significantly reduced intra- and interhemispheric FC, especially in the basal ganglia and thalamus, in patients with AS. Significant reductions in fractional anisotropy were found in the corpus callosum, cingulum, posterior limb of the internal capsules, and arcuate fasciculus in patients with AS. Quantitative structural analysis also showed gray matter volume loss of the basal ganglia and diffuse WM volume reduction in AS compared with the control group. CONCLUSIONS: This integrated quantitative MR imaging analysis demonstrated poor functional and structural connectivity, as well as brain volume reduction, in children with AS, which may explain the motor and language dysfunction observed in this well-characterized neurobehavioral phenotype.

Effect of ricin on biosynthesis of myeloma protein (IgA) and general cellular proteins in MOPC-315 cells.

Ricin, a phyto-toxin from the seeds of Ricinus communis, preferentially inhibits synthesis of myeloma protein by MOPC-315 cells as compared to the synthesis of general proteins. In contrast, cycloheximide inhibited equally both myeloma protein synthesis as well as general protein synthesis. These results suggest that proteins synthesized near or on cell membranes are more sensitive to Ricin which binds to the acceptor molecule on the plasma membrane.

Metabolism of ribosomal RNA in mutants of Escherichia coli doubly defective in ribonuclease III and the transcription termination factor rho.

To determine if proteins RNase III and rho, both of which can determine the 3' ends of RNA molecules, can complement each other, double mutants defective in these two factors were constructed. In all cases (four rho mutations tested) the double mutants were viable at lower temperatures, but were unable to grow at higher temperatures at which both of the parental strains grew. Genetic analyses suggested that the combinations of the rnc rho (RNase III-Rho-) mutations was necessary and probably sufficient to confer temperature sensitivity on carrier strains. Physiological studies showed that synthesis and maturation of rRNA, which is greatly affected by RNase III, as well as other RNAs, was indistinguishable in rnc rho strains as compared to rnc rho+ strains, thus suggesting that RNase III and rho do not complement one another in determining the 3' ends of RNA molecules. In rnc rho strains, however, the newly synthesized rRNA failed to accumulate. Thus, decay of rRNA could be the reason for the temperature sensitivity of the double mutant strains. These experiments suggest that RNase III and rho can both protect rRNA from degradation by cellular ribonucleases. They also point to the possibility that the nucleotide sequences involved in the determination of the 3' ends of RNA molecules by these two factors are not identical.

EEG and clinical predictors of medically intractable childhood epilepsy.

OBJECTIVES: To identify electroencephalographic and clinical factors associated with both seizure control and medical intractability in children with epilepsy. METHODS: We retrospectively reviewed EEGs and medical records from children with well-controlled epilepsy or medically intractable epilepsy. SUBJECTS: Features of the initial EEG and clinical findings were compared in 39 children with well controlled seizures and 144 with intractable epilepsy using both univariate and multivariate analyses. RESULTS: Strong univariate associates were noted between intractability and several EEG factors: abnormal EEG background including diffuse slowing, asymmetry, abnormal amplitude, a high frequency of spikes or sharp waves, and focal spike and wave activity. With multiple logistic regression, independent predictors of intractability were diffuse slowing and focal spike and wave activity. Strong univariate associates of clinical factors with intractability included: an early age of onset, simple partial, tonic, and myoclonic seizures, a history of status epilepticus, a symptomatic etiology of the seizures, and abnormal magnetic resonance imaging of the head. Multivariate analysis detected 4 independent clinical features associated with intractable epilepsy: symptomatic etiology, tonic seizures, simple partial seizures, and an early age of onset. CONCLUSIONS: There are a number of EEG and clinical features that can be identified early in the course of childhood epilepsy that are predictive of outcome. These findings will need to be verified in a prospective study.

Localized proton MR spectroscopy of the allocortex and isocortex in healthy children.

BACKGROUND AND PURPOSE: The human allocortex is different from the isocortex in neuroglial cytoarchitecture. The purpose of this study was to compare metabolic data of the allocortex with those of the isocortex by using localized proton MR spectroscopy. METHODS: Short-TE stimulated-echo acquisition mode proton MR spectroscopy (TR/TE = 3000/30) was applied to the allocortex of the temporal lobe and isocortex of the parietal or frontal lobe in 30 healthy children (19 boys and 11 girls, 3-14 years old). Peak intensities of N-acetylaspartate (NAA), choline-containing compounds (Cho), and myo-inositol (mI) relative to creatine and phosphocreatine (Cr) were calculated. Metabolic data from the investigated regions were compared. RESULTS: NAA/Cr was significantly lower in the allocortex than in the isocortex of the parietal or frontal lobe: 1.05 +/- 0.12 (n = 33) vs. 1.36 +/- 0.10 (n = 28) or 1.32 +/- 0.10 (n = 12), respectively. Cho/Cr and mI/Cr were significantly higher in the allocortex than in the isocortex: 0.84 +/- 0.11 vs. 0.56 +/- 0.06 or 0.75 +/- 0.10; 0.78 +/- 0.15 vs. 0.54 +/- 0.08 or 0.66 +/- 0.09, respectively. In the isocortex, NAA/Cr was not different but Cho/Cr and mI/Cr were significantly higher in the frontal cortex than in the parietal cortex. CONCLUSION: Clear metabolic differences were observed between the allocortex and isocortex.

Translucence stereoscopy of interictal magnetoencephalographic epileptiform discharge.

We have developed a translucence stereoscopy method for displaying the distribution of multiple interictal epileptiform discharges within the intracranial space. The epileptiform discharges, measured using a whole-head magnetoencephalography system, were modeled by a least-squares method to obtain the equivalent current dipoles. The dipoles were located in the stereo pair of intracranial images composed of translucent brain slices at several selected levels. The technique demonstrated clearly the distribution of interictal dipoles within the brain in three patients. Three dimensional understanding of the intracranial distribution of multiple dipoles in one image is valuable in analyzing the intracerebral neurophysiological events in epileptic patients.

Treatment of seizures in subcortical laminar heterotopia with corpus callosotomy and lamotrigine.

Focal and generalized cortical dysgeneses are sometimes seen on the magnetic resonance images (MRI) of patients with epilepsy. Subcortical laminar heterotopia are bilateral collections of gray matter in the centrum semiovale that resemble a band or "double cortex" on MRI. We studied one male and two female patients with subcortical laminar heterotopia who had moderate to severe developmental delay, early-onset epilepsy, and medically refractory seizures. Atonic, atypical absence, tonic, myoclonic, complex partial, and generalized tonic-clonic seizures were recorded. Interictal and ictal electroencephalographic patterns were generalized and, less commonly, multifocal. Two years after corpus callosotomy, one patient was free of generalized tonic-clonic and atonic seizures, but the other patient who had undergone callosotomy had no significant reduction in seizure frequency. With lamotrigine treatment, the patient who had not had surgery had complete cessation of monthly episodes of status epilepticus and a dramatic reduction of generalized tonic-clonic seizures, and the other patient who received lamotrigine had a 50% reduction of her atonic seizures. In patients with subcortical laminar heterotopia, atonic and generalized tonic-clonic seizures can be substantially reduced or eliminated by corpus callosotomy or treatment with lamotrigine.

Possible mechanism of E. coli messenger RNA degration: non-enzymatic degradation.

The present paper points out lack of evidence to support the presently prevailing concept that E. coli mRNA turnover, in the gene expression process, cannot take place without mRNase(s). The present paper draws attention to possible physicochemical factors involved in the degradation, and advances a notion of non-enzymatic spontaneous degradation of E. coli mRNA in its expression process. This suggested hypothesis helps to explain hitherto reported findings on the mode of E. coli mRNA degradation.

Complications and results of subdural grid electrode implantation in epilepsy surgery.

BACKGROUND: We assessed the risk of delayed subdural hematoma and other complications associated with subdural grid implantation. METHODS: Forty-nine patients underwent subdural grid implantation with/without subdural strips or depth electrodes from January 1994 to August 1998. To identify the risk associated with subdural grid implantation, a retrospective review of all patients' medical records and radiological studies was performed. RESULTS: The major complications of 50 subdural grid electrode implantations were as follows: four cases (7.8%) of delayed subdural hematoma at the site of the subdural grid, requiring emergency operation; two cases (3.9%) of infection; one case (2.0%) of epidural hematoma; and one case (2.0%) of brain swelling. After subdural hematoma removal, the electrodes were left in place. CCTV monitoring and cortical stimulation studies were continued thereafter. No delayed subdural hematoma has occurred since routine placement of subdural drains was begun. CONCLUSIONS: In our experience the worst complication of subdural grid implantation has been delayed subdural hematoma. Placement of subdural drains and close observation may be helpful to prevent this serious complication.

Characterization and expression of beta-1,3-glucanase genes in peach.

Beta-1,3-glucanase is one of the pathogenesis-related (PR) proteins involved in plant defense responses. A peach beta-1,3-glucanase gene, designated PpGns1, has been isolated and characterized. The deduced amino acid sequence of the product of PpGns indicates that it is a basic isoform (pI 9.8), and contains a putative signal peptide of 38 amino acids but has no C-terminal extension. Amino acid sequence comparisons revealed that PpGns1 is 69% and 67% identical to citrus and soybean beta-1,3-glucanases, respectively. Southern analysis of total genomic DNA also indicates that at least three genes for beta-1,3-glucanases exist in peach, forming a small gene family. Characterization of four additional clones by PCR has identified a second beta-1,3-glucanase gene, PpGns2. PpGns2 has been partially sequenced, and when compared to PpGns1, it shows high sequence homology, 96% and 99% nucleotide identity in the first and (partial) second exons, respectively. The deduced partial sequence of the PpGns2 product displays only two differences from PpGns1 in the signal peptide and one in the (partial) mature protein (141 amino acids). The 5'-flanking promoter regions of these two genes share 90% identity in nucleotide sequences interrupted by five major gaps (4-109 nt long). The promoter region contains various sequences similar to cis-regulatory elements present in different stress-induced plant genes. In leaves and stems of peach shoot cultures grown in vitro, PpGns1 is induced within 12 h after exposure to a culture filtrate of Xanthomonas campestris pv. pruni or ethephon. However, it is not induced following treatment with mercuric chloride.

Properties of acetylcholinesterase reconstituted in liposomes of a different charge.

Acetylcholinesterase (AChE) purified from mouse brain was reconstituted in liposomes of a different charge, and the properties of liposome-associated AChE were investigated. Relative to the Km value (38.5 microM) of AChE bound to a neutral liposome, the value of AChE reconstituted in a negatively-charged liposome decreased to 23.3 microM, whereas that of AChE in a positively-charged liposome increased to 90.9 microM. Additionally, AChE bound to a positively-charged liposome expressed a wider range of optimum pH than the enzyme in a negatively-charged liposome. In a stability study, it was found that soluble AChE was unstable at pH 5.5 and 7.4, while it was relatively stable at pH 10. Noteworthy, the immobilization of AChE to liposome enhanced the stability of soluble enzyme at acidic and neutral pH. Moreover, in the stabilization of the enzyme, a neutral liposome was more effective than charged liposomes, of which a positively-charged liposome was more effective than a negatively-charged liposome at acidic pH. Based on these results, it is proposed that while the Km value and the pH dependence of AChE activity are affected by the charge of liposome, the stability of AChE is determined mainly by a hydrophobic binding to a phospholipid membrane.

Cystic fibrosis--a case presented with recurrent bronchiolitis in infancy in a Korean male infant.

The aim of this case report is to draw the attention to the occurrence of cystic fibrosis (C.F.) in a Korean infant and thus increase the awareness for the diagnosis. The male infant was presented with a history of recurrent bronchiolitis manifested by severe cough, wheeze and dyspnea from three weeks of age, in whom the diagnosis of C.F. was clinically suspected and was confirmed by demonstration of two elevated sweat chloride levels (97 mEq/L and 99 mEq/L) in the patient. The diagnosis was delayed because the main manifestations of C.F. were the same as the main symptoms of common diseases such as cough, diarrhea and failure to thrive. C.F. is probably underdiagnosed in Korean population both because the diagnosis is not considered since the disease is thought to be uncommon or even not to occur and because diagnostic facilities including the quantitative iontophoresis sweat test are lacking.

Hallervorden-Spatz syndrome in two siblings diagnosed by the clinical features and magnetic resonance imaging (MRI).

Hallervorden-Spatz syndrome (HSS) is a heredodegenerative disorder characterized by both progressive pyramidal and extrapyramidal signs, dysarthric speech, and mental deterioration. No diagnostic biochemical test is yet available, and diagnosis of HSS can be confirmed only at autopsy by the characteristic neuropathology including abnormal iron storage, disordered myelination, and loss of brain substance. We present two siblings with clinical features consistent with HSS, in whom magnetic resonance imaging (MRI) demonstrated the deposition of iron in the globus pallidus and the substantia nigra thus allowing an antemortem diagnosis of HSS.