Biomedical subjects

Yoshihisa Sugimoto

Publications and source records attributed to Yoshihisa Sugimoto.

6 recordsLinked to original sources

PubMed2006

Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a distinct form of idiopathic generalized epilepsy (IGE). One of the candidate regions for human JME has been mapped on chromosome band 6p11-p12 by linkage analyses and is termed EJM1 (MIM 254770). Recently, we reported the reduction of the EJM1 region to 3.5cM that contains 18 genes, the exclusion of three genes (LRRC1, GCLC, KIAA0057) by mutation analyses, and the identification of Myoclonin1/EFHC1 as the EJM1 gene. Here, we describe detailed physical and transcriptome maps of the 3.5cM EJM1 region, and detailed results of mutation analyses for the remained 14 genes (HELO1, GCMA, KIAA0936, FBXO9, GSTA3, GSTA4, PTD011, KIAA0576, LMPB1, IL17F, MCM3, PKHD1, KIAA0105, TFAP2B) in patients with JME. We identified 49 single nucleotide changes in eight genes. Twelve amino acid substitutions occurred in two genes, 11 silent mutations in seven genes, and 26 in the non-coding or intronic regions of seven genes. Twelve amino acid substitutions in the two genes (IL17F, PKHD1) were also observed in healthy control individuals or did not co-segregate with the disease phenotypes in other family members. Thus, the absence of significant and potentially functional mutations in the remaining 14 genes further supports the concept that Myoclonin1/EFHC1 is the EJM1 gene in chromosome 6p12.

Chromosomes, Human, Pair 6↗

PubMed2006

Lateral and posterior pillar grade changes during the treatment of Perthes disease in older patients using skin traction and range of motion exercises.

INTRODUCTION: The lateral pillar (LP) grade changes detected during treatment periods have received a lot of attention recently. Lappin et al. reported LP collapses in 92 of 275 (33%) patients during the treatment, but did not provide information for comparing treatment methods and age of onset of the disease. The purpose of this study was to review radiological changes in LP grade in older patients with Perthes disease during 20 months of treatment with skin traction and ROM exercises. We have also reported any grade changes in the posterior pillar (PP) classification. MATERIAL AND METHODS: Twenty-one patients with unilateral disease who were 9 years or older at the onset of symptoms had been followed until skeletal maturity. RESULTS: Out of 21 older patients with Perthes disease, our study had two (9.5%) who experienced LP collapse and two (9.5%) who experienced PP collapse during the first 20 months of treatment. The average time from onset to hospitalization in hips, initially classified as LP group C and PP group C, was significantly longer than in LP and PP groups A and B. The LP collapse in two hips and PP collapse in two hips occurred during months 4-8 of treatment. On the other hand, of the patients allowed to ambulate with the Pogo stick orthosis from months 8 to 12 and without a brace from months 10 to 15, none had a collapse of their LPs or PPs during these periods. CONCLUSION: Lappin et al. reported that 92 of 275 patients (33%) who were managed conservatively in several hospitals experienced LP collapse during their treatment periods. Our results suggest that older patients with this disease treated with skin traction and ROM exercises rarely suffer a LP collapse, as compared with the Lappin et al. report.

Adolescent↗

PubMed2006

Surgical results of sacral perineural (Tarlov) cysts.

The purpose of this study was to investigate the surgical outcomes and to determine indicators of the necessity of surgical intervention. Twelve consecutive patients harboring symptomatic sacral perineural cysts were treated between 1995 and 2003. All patients were assessed for neurological deficits and pain by neurological examination. Magnetic resonance of imaging, computerized tomography, and myelography were performed to detect signs of delayed filling of the cysts. We performed a release of the valve and imbrication of the sacral cysts with laminectomies in 8 cases or recapping laminectomies in 4 cases. After surgery, symptoms improved in 10 (83%) of 12 patients, with an average follow-up of 27 months. Ten patients had sacral perineural cysts with signs of positive filling defect. Two (17%) of 12 patients experienced no significant improvement. In one of these patients, the filling defect was negative. In conclusion, a positive filling defect may become an indicator of good treatment outcomes.

Adult↗

PubMed2004

Mutations in EFHC1 cause juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.

Animals↗

PubMed2002

Identification and mutational analysis of candidate genes for juvenile myoclonic epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5.

Juvenile myoclonic epilepsy (JME) is one of the most frequent hereditary epilepsies characterized by myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Genetic studies have revealed four major chromosomal loci on 6p21.3, 6p11-12, 6q24, and 15q14 as candidate regions harboring genes responsible for JME. Previously we reported the region on 6p11-p12 (EJM1), and here we report the identification and mutational analysis of candidate genes for EJM1. One of those is a leucine-rich repeat-containing 1 (LRRC1) gene that is composed of 14 exons and codes for 524 amino acid residues. In Northern analysis, 7 kb transcripts of LRRC1 gene were detected in multiple tissues, most strongly, in heart, lung, and kidney. Mutation analysis of LRRC1 gene in 20 JME patients from ten families revealed one nucleotide substitution that lead to amino acid exchange (c.577 A>G; Ile193Val). This variation, however, did not co-segregate with the disease phenotype. We further performed mutational analyses of CLIC5, KIAA0057 and GCLC genes in or flank to the EJM1 region. These analyses did not provide any evidences that these genes are responsible for the JME phenotype, and suggested that these may not be the EJM1 gene.

Base Sequence↗

PubMed2002

An experimental study on the perineurial window.

Neurological symptoms of herniated nerve fibers resulting from limited perineurial injury from sharp materials such as needles have become a recent topic in clinical practice. However, the mechanism of this disorder, which is known as a perineurial window, has not been clarified. To investigate the mechanism of nerve damage in the perineurial window, we designed small (1-mm length) and large (5-mm length) perineurial windows using tibial nerves of Wistar rats. In the 1-mm group, a marked hernia of the endoneurial contents developed soon and decreased in size with time, but protrusion of nerve fibers was still observed after 12 weeks. Nerve fibers in both the herniated portion and under the edge of the window were damaged. Even after 12 weeks, regeneration of the nerve fibers and the perineurium was incomplete. In contrast, in the 5-mm group, the initial endoneurial edema was remarkable, but herniated nerve fibers were not seen after 12 weeks. Neurological impairment in the 5-mm group was marked in the early stage but rapidly recovered. The repair of the perineurium and nerve fibers in the 1-mm group was slower than in the 5-mm group. Persistent neurological symptoms in the perineurial window appeared to be more closely associated with entrapment of nerve fibers at the window edge rather than with disruption of endoneurial homeostasis.

Animals↗