Abnormal maturation and differentiation of neocortical neurons in epileptogenic cortical malformation: unique distribution of layer-specific marker cells of focal cortical dysplasia and hemimegalencephaly.

Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are major causes of intractable epilepsy in children. The probable pathogenesis of FCD and HMG is the abnormal migration and differentiation of neurons. The aim of the present study was to clarify the abnormal cytoarchitecture, based on neuronal immaturation. Tissue samples were obtained from 16 FCD and seven HME patients, aged between 2 months and 12 years, who had been diagnosed as typical FCD and HME, following surgical treatment for intractable epilepsy. Paraffin-embedded sections were stained with the antibodies of three layer-markers that are usually present only during the fetal period, namely SATB2 (expressed in the upper layer of the normal fetal neocortex), FOXP1 (expressed in the 5th layer), and TBR1 (expressed in the 6th layer). In FCD, SATB2-positive (+) cells located in the middle and deep regions of FCD Ia and Ib, but only in the superficial region of FCD IIa and IIb. FOXP1+ cells diffusely located in the neocortex, especially the upper layer of FCD IIa and IIb. TBR1+ cells mainly located in the middle and deep regions, and also white matter. In FCD IIb, TBR1+ cells were in the superficial region. In HME, SATB2+ and FOXP1+ cells were found diffusely. TBR1+ cells were in the middle and deep regions. On the basis of continued expression of fetal cortical layer-specific markers in FCD and HME brains, the abnormal neocortical formation in both is likely to be the result of disrupted neuronal migration and dysmaturation. The expression pattern is different between FCD and HME.

Abnormal maturation of non-dysmorphic neurons in focal cortical dysplasia: immunohistochemical considerations.

AIM: Dysmorphic neurons and balloon cells in focal cortical dysplasia (FCD) reportedly show immaturity and abnormal differentiation with neuronal and glial components. Although normal-looking neurons (NL-neurons) in FCD are major constituent elements, their biological characteristics have never been identified. The aim of this study was to investigate maturation of NL-neurons with the focus on neuronal developmental lineage. METHODS: Eighteen FCD surgical specimens and controls were examined immunohistochemically using the antibodies for nestin, mammalian achaete-scute complex homolog 1 (Mash1), prospero-related homeobox 1 (Prox1), neuron-specific beta-III tubulin (Tuj1) and microtubule-associated protein 2 (MAP2) of neuronal lineage, glutamic acid decarboxylase (GAD), calretinin (CR) and calbindin (CB) of interneuron markers, and glial fibrillary-acidic protein (GFAP) of glial cell marker. Additionally, we performed fluorescent-double staining with these markers, and semi-quantitative analysis. RESULTS: NL-neurons in FCD had both mature and immature components, without interneuron components. NL-neurons in FCD showed abnormal maturation with the combined expression of MAP2 and Mash1/Prox1. Prox1-containing cell distribution in the deep layer was different from that of Mash1-containing cells in the superficial area. The MAP2-containing cell concentration decreased in the order of type I-A, I-B, II-A and II-B, but the Tuj1-containing cell concentration increased. CONCLUSION: These findings may reflect differences in neuronal function and expression timing in developmental stages. From the standpoint of molecular expression, abnormal maturation of NL-neurons may initiate synaptic dysfunction, resulting in intractable seizures of FCD.

[Serious complications of intraventricular interferon-alpha and ribavirin in the treatment of subacute sclerosing panencephalitis].

We treated three patients with subacute sclerosing panencephalitis with intraventricular interferon-alpha and oral inosiplex, and followed their clinical courses. One patient was also treated with ribavirin. Results were unsatisfactory; no significant clinical improvement was seen in the patients, and a number of serious complications occurred. Malfunction of the Ommaya reservoir, septic meningitis and chemical encephalopathy were observed in the three patients, respectively. The use of intraventricular interferon-alpha and ribavirin therapy has been increasing despite insufficient evidence of its efficacy. A high risk of serious side effects exists with this therapy. Thus it is important to consider not only the effects but also the side effects and complications as described above. We also propose that a standard protocol for the use of interferon-alpha and ribavirin and the cessation of current therapy is necessary.

Nemaline (actin) myopathy with myofibrillar dysgenesis and abnormal ossification.

We report a 2-year-old boy who presented with marked hypotonia and was dependent on artificial ventilation since birth. He was diagnosed with nemaline (actin) myopathy, based on the cytoplasmic accumulation of thin filament aggregates and marked myofibrillar dysgenesis. Intranuclear rods and dispersed tiny nemaline bodies were also observed. The patient was shown to be heterozygous for a de novo mutation, c.430C>T (p.Leu144Phe), in the alpha-actin (ACTA1) gene. He also showed orbital osteosclerosis, longitudinal striations of the iliac bones, hepatomegaly, undescended testis, a unilateral vesico-ureteric stenosis, severe failure to thrive, and dilatation of the lateral cerebral ventricles. Besides the severe muscle involvement, these clinical findings further broaden the clinical spectrum of actinopathy phenotypes.

Conformational analysis of 1-butyl-3-methylimidazolium by CCSD(T) level ab initio calculations: effects of neighboring anions.

Conformational energies for the butyl group of 1-butyl-3-methylimidazolium (bmim) were calculated by high-level ab initio methods. Estimated relative energies for the TT, GT and G'T rotamers of an isolated bmim cation at the CCSD(T)/cc-pVTZ level are 0.0 -0.02 and -0.50 kcal/mol, respectively. The close contact of a Cl anion to theC(2)-H of imidazolium considerably increases the relative stability of the GT rotamer. Estimated relative energies for the three rotamers of the [bmim]Cl complex, in which the Cl anion exists close to the C(2)-H, are 0.0, -1.61 and -0.25 kcal/mol, respectively. The GT rotamer is favored by the strong attractive electrostatic interaction between the bmim cation and Cl anion. The C(2)-H group in the GT rotamer has a larger positive charge compared with those in the TT and G'T rotamers. The contact of a Br anion to the C(2)-H also stabilizes the GT rotamer. The effects of the Cl anion close to the C(4)-Hand C(5)-Hare small. The anion effects suggest that the GT rotamer is the most stable in ionic liquids. The positive charge on imidazolium ring does not largely change the conformational energies. Estimated relative energies for the three rotamers of N-butylimidazole (0.0, -0.29 and -0.75 kcal/mol, respectively) are not largely different from those for isolated bmim. Calculated MP2/cc-pVTZ level torsional potential for the C im-N im-C-C bond has a minimum when the torsional angle is close to 90 degrees. Coplanar conformation is not a stable structure. Calculated torsional barrier height between the two nonplanar minima is less than 1 kcal/mol.

Density dependences of long-range fluctuations and short-range correlation lengths of CHF3 and CH2F2 in supercritical states.

Small-angle x-ray scattering (SAXS) measurements are carried out for supercritical polar fluorocarbons, CHF3 and CH2F2, along the isotherm of 1.04 in reduced temperatures with the density range from 0.3 to 1.5 in reduced units. A novel apparatus for determination of absorption factors of the sample fluids is used in the present measurements. The apparatus enables us to detect simultaneously the accurate factors during the observation of the SAXS signals. Long-range fluctuations such as density fluctuations and correlation lengths are evaluated from the obtained SAXS data. The reduced correlation lengths are obtained by normalization by each molecular size, in order to discuss the fluctuations independent of the difference of the individual molecular size. The density fluctuations and the reduced correlation lengths of CHF3 and CH2F2 are compared with those of CO2 and H2O. The results are as follows: H2O>CH2F2>CHF3 approximately CO2 in the order of magnitude. The fluctuations of CH2F2 are significantly distinguishable from those of CHF3 and show intermediate aspect between H2O and a group of CO2 and CHF3. In addition, the short-range correlation lengths, i.e., the Ornstein-Zernike direct correlation lengths, are firstly discussed from both viewpoints of density and substance dependences. The reduced short-range correlation lengths normalized by individual molecular size are found to trace a universal curve as a function of the reduced density.