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A 22-month-old toddler presented with involuntary movements, hemiparesis, and behavioral changes. Magnetic resonance imaging showed no abnormality, but positron emission tomography (PET) showed focal hypermetabolism. By immunohistochemical technique with the patient's sera in control brain sections, autoantibodies recognizing the same areas as found by PET scanning were identified and disappeared after intravenous immunoglobulin therapy. PET scanning may be useful in the diagnosis of autoimmune encephalitis.

Aim: This study assessed changes in depressive tendency of children with growth hormone deficiency., Methods: The 41 children with growth hormone deficiency were assessed using the Depression Self-Rating Scale for Children. A score of 16 or more indicated a depressive tendency. The first assessment was carried out before growth hormone treatment, and the second one was carried out at 6 months or longer after the beginning of growth hormone treatment., Results: The Depression Self-Rating Scale for Children improved significantly from 9.7 +/- 6.1 points before treatment to 6.9 +/- 4.6 points after treatment (P= 0.0013). A depressive tendency was observed in six patients (15%) before growth hormone treatment, and in two patients (5%) after treatment. No significant relationship was observed between the decrease in the score and the length of the treatment. A significant improvement was observed for 6 of the 18 items in the Depression Self-Rating Scale for Children., Conclusion: A depressive tendency was relatively common in children with growth hormone deficiency, and the Depression Self-Rating Scale for Children was decreased after growth hormone treatment. These results suggest that growth hormone treatment may have positive effects on the psychosocial aspects in children with growth hormone deficiency.

Background: DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through web browsers using accession numbers (IDs) or keywords, but gene-expression patterns are not considered when retrieving such data. The Connectivity Map was recently introduced to compare gene expression data by introducing gene-expression signatures (represented by a set of genes with up- or down-regulated labels according to their biological states) and is available as a web tool for detecting similar gene-expression signatures from a limited data set (approximately 7,000 expression profiles representing 1,309 compounds). In order to support researchers to utilize the public gene expression data more effectively, we developed a web tool for finding similar gene expression data and generating its co-expression networks from a publicly available database., Results: GEM-TREND, a web tool for searching gene expression data, allows users to search data from GEO using gene-expression signatures or gene expression ratio data as a query and retrieve gene expression data by comparing gene-expression pattern between the query and GEO gene expression data. The comparison methods are based on the nonparametric, rank-based pattern matching approach of Lamb et al. (Science 2006) with the additional calculation of statistical significance. The web tool was tested using gene expression ratio data randomly extracted from the GEO and with in-house microarray data, respectively. The results validated the ability of GEM-TREND to retrieve gene expression entries biologically related to a query from GEO. For further analysis, a network visualization interface is also provided, whereby genes and gene annotations are dynamically linked to external data repositories., Conclusion: GEM-TREND was developed to retrieve gene expression data by comparing query gene-expression pattern with those of GEO gene expression data. It could be a very useful resource for finding similar gene expression profiles and constructing its gene co-expression networks from a publicly available database. GEM-TREND was designed to be user-friendly and is expected to support knowledge discovery. GEM-TREND is freely available at http://cgs.pharm.kyoto-u.ac.jp/services/network.

G-protein coupled receptors (GPCRs) represent one of the most important families of drug targets in pharmaceutical development. GLIDA is a public GPCR-related Chemical Genomics database that is primarily focused on the integration of information between GPCRs and their ligands. It provides interaction data between GPCRs and their ligands, along with chemical information on the ligands, as well as biological information regarding GPCRs. These data are connected with each other in a relational database, allowing users in the field of Chemical Genomics research to easily retrieve such information from either biological or chemical starting points. GLIDA includes a variety of similarity search functions for the GPCRs and for their ligands. Thus, GLIDA can provide correlation maps linking the searched homologous GPCRs (or ligands) with their ligands (or GPCRs). By analyzing the correlation patterns between GPCRs and ligands, we can gain more detailed knowledge about their conserved molecular recognition patterns and improve drug design efforts by focusing on inferred candidates for GPCR-specific drugs. This article provides a summary of the GLIDA database and user facilities, and describes recent improvements to database design, data contents, ligand classification programs, similarity search options and graphical interfaces. GLIDA is publicly available at http://pharminfo.pharm.kyoto-u.ac.jp/services/glida/. We hope that it will prove very useful for Chemical Genomics research and GPCR-related drug discovery.

Status epilepticus (SE) occurs in children of all ages. Recent epidemiologic investigations of SE show heightened morbidity and mortality in newborns and young infants. However, the existing definition of SE in newborns is not precise and not easily applied in clinical investigations or in clinical practice. To evaluate the underlying conditions, clinical features and treatment of SE in neonates in Japan, a retrospective multi-center study was performed. In the initial investigation, questionnaires were sent to pediatric neurologists in 194 neonatal intensive care units of university hospitals, children's hospitals, and general hospitals throughout in Japan. The questionnaires sought information on the background of each case, types of seizures, etiology of SE, treatments, results and adverse effects of treatment for patients less than 1 week old who had prolonged or frequently repeated seizures lasting more than 15 min and who are refractory to treatment with conventional anticonvulsants, such as diazepam (DZP), phenobarbital (PB) or phenytoin (PHT). As a secondary investigation, 65 cases from nine institutes, which completely fulfilled these criteria and were treated with midazolam (MDL) or lidocaine (Lid) to stop seizures were examined more fully. Subtle seizure and generalized tonic-clonic seizure were the most frequent seizure types. Neonatal SE was most frequently associated with hypoxic-ischemic encephalopathy, followed by intraventricular hemorrhage, central nervous system infections, and cerebral infarction. The final treatment outcome was available for 72.7% and 81.3% of MDL- and Lid-treated patients, respectively. Adverse effects of MDL and Lid were identified in 7.3% and 6.3% of patients, respectively. To reveal electroclinical seizures, clinical seizures without ictal discharge or other non-epileptic movements in neonates was important for appropriate treatment. MDL and Lid were useful drugs for the treatment of neonatal SE.

Background: In class prediction problems using microarray data, gene selection is essential to improve the prediction accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVM-RFE) has become one of the leading methods and is being widely used. The SVM-based approach performs gene selection using the weight vector of the hyperplane constructed by the samples on the margin. However, the performance can be easily affected by noise and outliers, when it is applied to noisy, small sample size microarray data., Results: In this paper, we propose a recursive gene selection method using the discriminant vector of the maximum margin criterion (MMC), which is a variant of classical linear discriminant analysis (LDA). To overcome the computational drawback of classical LDA and the problem of high dimensionality, we present efficient and stable algorithms for MMC-based RFE (MMC-RFE). The MMC-RFE algorithms naturally extend to multi-class cases. The performance of MMC-RFE was extensively compared with that of SVM-RFE using nine cancer microarray datasets, including four multi-class datasets., Conclusion: Our extensive comparison has demonstrated that for binary-class datasets MMC-RFE tends to show intermediate performance between hard-margin SVM-RFE and SVM-RFE with a properly chosen soft-margin parameter. Notably, MMC-RFE achieves significantly better performance with a smaller number of genes than SVM-RFE for multi-class datasets. The results suggest that MMC-RFE is less sensitive to noise and outliers due to the use of average margin, and thus may be useful for biomarker discovery from noisy data.

Microarray techniques provide new insights into molecular classification of cancer types, which is critical for cancer treatments and diagnosis. Recently, an increasing number of supervised machine learning methods have been applied to cancer classification problems using gene expression data. Support vector machines (SVMs), in particular, have become one of the most effective and leading methods. However, there exist few studies on the application of other kernel methods in the literature. We apply a kernel subspace (KS) method to multiclass cancer classification problems, and assess its validity by comparing it with multiclass SVMs. Our comparative study using seven multiclass cancer datasets demonstrates that the KS method has high performance that is comparable to multiclass SVMs. Furthermore, we propose an effective criterion for kernel parameter selection, which is shown to be useful for the computation of the KS method.

In general, epileptic seizures become more serious following infections. However, transient and permanent improvement of epileptic seizures has been observed following acute viral infections, without a recent change in anti-epileptic therapy. Questionnaires were sent to 73 institutions, throughout Japan, where pediatric neurologists care for children with epilepsy to characterize this phenomenon through clinician survey. Completed surveys were received from 11 institutions, and 21 cases were selected for the study. The age of the patients were 6 months to 17 years. The West syndrome or epilepsy subsequent to West syndrome cases were 16 out of 21. Two cases of symptomatic generalized epilepsy and one case each of symptomatic partial epilepsy, continuous spike-waves of slow sleep and severe myoclonic epilepsy in infancy were also reported. These seizures disappeared within 2 weeks subsequent to viral infections such as, exanthema subitum, rotavirus colitis, measles and mumps. The disappearance of intractable epileptic seizures following acute viral infections might be related to the inflammatory processes or the increased levels of antibodies after viral infections.

The infants' brain during the prenatal, perinatal and neonatal periods is susceptible to injury. Many problems in the perinatal period often result in bleeding, ischemia and other pathological changes in the infant brain. Which can subsequently cause cerebral palsy or developmental disorders. Unless they are discovered early and measures are taken, permanent brain damage may remain. Although neurological examinations at this stage is very difficult, it is very important to be familiar with neurological signs and assessment of extremely and very low birth weight infants and to discover early any abnormal findings of diseases such as neonatal asphyxia, intraventricular haemorrhage, periventricular leukomalacia, neonatal seizures and hydrocephalus.

A male neonate was admitted because prenatal ultrasonography indicated central nervous system abnormalities. Neurological examination showed no abnormality except for electroencephalographic spike activities. Magnetic resonance imaging revealed a cystic lesion in the left interhemispheric fissure, agenesis of the corpus callosum, and microgyria in the left frontotemporal lobes. Cerebral blood flow (CBF) was diffusely reduced. The cyst wall was partially removed and a cyst-peritoneal shunt procedure was performed. The histological diagnosis was glioependymal cyst. The spike activity disappeared and CBF dramatically improved after the operation.

Background: To determine the usefulness of a few types of photic stimulation in patients with photo-convulsive response., Methods: A clinical electroencephalographic study was conducted in nine children who developed convulsions and other symptoms while they watched the TV animation and were subsequently treated at the hospital. Photic stimulation was applied with their eyes open or closed. Another photic stimulation was applied with the video tape of the animation., Results: A photoparoxysmal response (PPR) was never seen in the electroencephalographs (EEG) in any of these patients when photic stimulation was applied with their eyes closed, while PPR was seen in three of seven patients when photic stimulation was applied with their eyes open. Two patients (siblings) showed no specific abnormality when photic stimulation was applied with their eyes either open or closed. However, myoclonus and PPR appeared when the EEG was conducted while they watched the video tape of the animation under supervised conditions., Conclusions: In a society where people are exposed to abundant TV games, TV animation or videos, self-restraint or regulations of frequent use of flickering scenes is thought to be necessary. However, it is also thought to be necessary to conduct EEG by applying photic stimulation, not only with the eyes closed, but also with the eyes opened or by applying flickering red light stimulation, which is emitted from a strong light source, or a combination of two colors, such as red and blue or red and green, in patients with suspected photosensitivity.

We report a case of linear nevus sebaceous syndrome with seizure, mental retardation, and hemiparesis. Magnetic resonance imaging (MRI) clearly demonstrated associated brain malformations of unilateral megalencephaly with cortical dysplasia and white matter change ipsilateral to the sebaceous nevi of the face and neck. Although magnetic resonance angiography (MRA) demonstrated only distortion of the main cerebral arteries without any occlusive or dysplastic findings, single photon emission computed tomography (SPECT) using [123I]N-Isopropyl-p-iodoamphetamine (IMP) revealed hypoperfusion in the affected cerebral hemisphere.

1) CZP had marked effects on RD. RD disappeared in 8 (73%) of 11 patients treated with CZP alone and 6 (43%) of 14 treated with CZP in combination with other drugs. Even when RD persisted, its amplitude and frequency decreased in some patients. 2) In the group treated with CZP in combination with other drugs, RD disappeared in all 5 patients with the persistent RD, of whom 2 had arachnoid cyst. Of the 6 patients with frequent seizures, 2 were subsequently diagnosed as having CPS and SPS, respectively. Patients who did not respond to CPZ included those in whom the diagnosis of BECCT should be reconfirmed, and electro-clinical response may be also useful for diagnosing RD. 3) In patients treated with CZP alone for a short-term treatment of BECCT, the drug administration could be discontinued only in one. A longer follow-up study is necessary to reach a conclusion in future.

Two patients with hypothyroidism had detectable serum levels of thyrotropin binding inhibitor immunoglobulin (TBII). Patient 1 was a newborn infant who had transient neonatal hypothyroidism due to transfer of TBII from the mother with nongoitrous autoimmune thyroiditis. Patient 2 was an 8-year-old girl with Down's syndrome who presented with signs of myxedema and central precocious puberty. She had no goiter, and the recognition of thyroid disease was delayed; the histological diagnosis of chronic lymphocytic thyroiditis was established by aspiration biopsy, and TBII had strong thyroid adenyl cyclase-inhibiting activity in vitro. It appears that TBII may be pathogenetically important for occurrence of neonatal hypothyroidism and nongoitrous autoimmune thyroiditis without goiter.

The unconjugated and conjugated bile acid levels in sera of 98 normal children and nine normal adults were measured by high performance liquid chromatography. The results showed that the mean total bile acid level was high, 11.0 +/- 8.7 mumol/liter (1 SD) during the neonatal period (0-4 wk) and then gradually decreased with age. The ratio of the concentration of conjugated bile acids to total bile acids in serum was as high as 90% or more in infants under 1 yr of age and slowly decreased with age. The mean ratio of cholic acid to chenodeoxycholic acid was high (1.7 +/- 1.1) during the neonatal period but decreased after 3 months to the adult level (0.4 +/- 0.2). The mean ratio of glycine conjugated bile acids to taurine conjugated bile acids was 3.0 +/- 3.1 during the neonatal period and the ratio during the 1st month of life was significantly lower than that after that period with little further change at any age. The mean ratio of the concentration of secondary bile acids to primary bile acids showed significantly lower values in infants less than 1 yr of age. The main bile acid was glycocholic acid in the neonatal period but after 1-3 months glycochenodeoxycholic acid predominated. With age, the serum bile acid pattern which was characteristic in infancy gradually approached that of adults.