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Iida A.,RIKEN | Takahashi A.,RIKEN | Kubo M.,RIKEN | Saito S.,RIKEN | And 25 more authors.
Human Molecular Genetics | Year: 2011

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Several susceptibility genes for ALS have been reported; however, ALS etiology and pathogenesis remain largely unknown. To identify further ALS-susceptibility genes,we conducted a large-scale case-control association study using gene-based tag single-nucleotide polymorphisms (SNPs). A functional SNP (rs2275294) was found to be significantly associated with ALS through a stepwise screening approach (combined P 5 9.3 3 10210, odds ratio 5 1.32). The SNP was located in an enhancer region of ZNF512B, a transcription factor of unknown biological function, and the susceptibility allele showed decreased activity and decreased binding to nuclear proteins. ZNF512B over-expression increased transforming growth factor-b (TGF-b) signaling, while knockdown had the opposite effect. ZNF512B expression was increased in the anterior horn motor neurons of the spinal cord of ALS patients when compared with controls. Our results strongly suggest that ZNF512B is an important positive regulator of TGF-b signaling and that decreased ZNF512B expression increases susceptibility to ALS. © The Author 2011. Published by Oxford University Press. All rights reserved.


Iida A.,RIKEN | Takahashi A.,RIKEN | Deng M.,Peking University | Zhang Y.,Peking University | And 18 more authors.
Neurobiology of Aging | Year: 2011

We performed a replication study of the 2 genetic variants, rs2814707 on 9p21.2 and rs12608932 on 19p13.3 that are recently reported to be most significantly associated with sporadic amyotrophic lateral sclerosis (ALS) in Caucasians. Both rs12608932 and rs2814707 showed no evidence of association in Japanese and Chinese (rs12608932, combined p = 0.58, odds ratio [OR] = 1.03, 95% confidence interval [CI] 0.93-1.13; rs2814707, combined p = 0.88, OR = 1.10, 95% CI 0.93-1.30). The association of these loci with susceptibility to sporadic ALS is considered negative in East Asians. © 2011 Elsevier Inc.


Kasahata N.,Chigasaki Tokushukai General Hospital | Kasahata N.,Tokyo Metropolitan Ohtsuka Hospital | Kasahata N.,Tokyo Metropolitan Institute of Medical Science | Uchihara T.,Tokyo Metropolitan Institute of Medical Science | And 3 more authors.
Brain Pathology | Year: 2012

A 71-year-old female developed dementia, supranuclear gaze palsy, pseudobulbar palsy, dorsiflexion of neck, rigidity of neck, absence of tremor or cog-wheel rigidity of extremities, and postural reflex disturbance. Levodopa/carbidopa prescribed without clinical improvement. Sudden cardiopulmonary arrest on the 24th hospital day was followed by repeated respiratory infection until she died on the 58th hospital day. Ischemic changes were scattered in entire cerebral cortices, putamen, external part of globus pallidus, substantia nigra, pontine nuclei, and cerebellum. Furthermore, Lewy bodies were detected in the substantia nigra, oculomotor nucleus, loci cerulei, and dorsal motor nucleus of vagus. Gallyas-silver impregnation demonstrated argyrophilic structures around hypoxic ischemic foci: the putamen, dentate gyrus and CA4 of hippocampus, cerebral cortices, Purkinje cells, substantia nigra and subthalamic nucleus. These Gallyas-positive structures were 1) negative for AT8, 2) granular in cytoplasm without fibrillary structure, 3) abundant around ischemic foci. Typical tuft-shaped astrocytes were absent. Because trivial ischemic lesions are one of the most frequent findings in human autopsy brains, it is worth paying attention to possible induction of Gallyas-positive structures around ischemic foci for correct interpretation. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.


Iida A.,RIKEN | Hosono N.,RIKEN | Sano M.,Chibanishi General Hospital | Kamei T.,Chigasaki Tokushukai General Hospital | And 6 more authors.
Neurobiology of Aging | Year: 2012

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective motor neuron death in the brain and spinal cord. Many disease genes for ALS have been identified; however, each disease gene is responsible for very small fractions of ALS. Recently, mutations of the gene encoding optineurin (. OPTN) are reported in familial and sporadic ALS. . OPTN is also responsible for a small number of ALS, 3.8% of familial and 0.29% of sporadic ALS in Japanese. The low prevalence may be an underestimation due to incomplete screening of the mutation. To examine . OPTN mutations more extensively, we screened the . OPTN deletions using a quantitative PCR system. We examined 710 Japanese ALS subjects who had previously been found to have no . OPTN mutations by a screening using a PCR-direct sequence strategy. We identified 3 kinds of deletions in 5 patients; one was homozygous, and the remaining were heterozygous. All deletions occurred due to the Alu-mediated recombination and are expected to result in null alleles. Our results suggest that the . OPTN deletion mutation in ALS is not infrequent and the prevalence of the . OPTN mutation in Japanese sporadic ALS is considerably high. © 2012 Elsevier Inc..


Iida A.,RIKEN | Kamei T.,Chigasaki Tokushukai General Hospital | Sano M.,Chibanishi General Hospital | Oshima S.,Chiba Tokushukai Hospital | And 4 more authors.
Neurobiology of Aging | Year: 2012

Mutations in TARDBP encoding TDP (TAR DNA binding protein)-43 have been reported in familial and sporadic amyotrophic lateral sclerosis (ALS), but mostly in Caucasians. In other ethnic groups, four types of mutations are found in familial ALS. In sporadic ALS, the TARDBP mutations frequency is low in Caucasians (0-5%) and no mutation has been found in other ethnic groups. To examine spectrum of TARDBP mutations and its frequency in Japanese, we screened the TARDBP mutation in 721 Japanese ALS by direct sequencing. We identified a novel mutation, c.1069G > A (p.Gly357Ser) and a known mutation in sporadic ALS. One patient was homozygous for p.Gly357Ser, which was the first for TARDBP mutation. Our study showed that TARDBP mutations also occur in non-Caucasian sporadic ALS. The estimated frequency of the TARDBP mutation in sporadic ALS is 0.29% in Japanese. The mutation frequency in familial ALS in Japanese is also similar to that in Caucasian, and is ~10 times higher than that in Japanese sporadic ALS. © 2012 Elsevier Inc.


Watanabe K.,Chigasaki Tokushukai General Hospital
Japanese Journal of Medical Mycology | Year: 2014

We report two cases of dermatophytosis caused by Microsporum (M.) gypseum. One case was a 59-yearold healthy womanwho complained of itchy annular erythema onher right forearm. We isolated M. gypseum from scales onthe forearm. The other case was a 73-year-old midwife who had developed infiltrated erythema onher face for 6 months. M. gypseum was isolated from scales of the nose. Both womenl iked gardening and M. gypseum was isolated from the gardenso il of these womenby a hair-baiting technique. The first case had a cat, a mouse and an owl, and the second had a dog. Hairbrush culture of these pets, however, was negative. So we concluded both cases were infected with M. gypseum from gardenso il. We isolated M. gypseum from soil collected inCh igasaki city. Of the 7 fungal cultures from 10 samples, 2 cultures were identified as M. gypseum. © 2014, Japanese Society for Medical Mycology. All rights reserved.


PubMed | Chigasaki Tokushukai General Hospital
Type: Case Reports | Journal: Medical mycology journal | Year: 2014

We report two cases of dermatophytosis caused by Microsporum (M.) gypseum. One case was a 59-year-old healthy woman who complained of itchy annular erythema on her right forearm. We isolated M. gypseum from scales on the forearm. The other case was a 73-year-old midwife who had developed infiltrated erythema on her face for 6 months. M. gypseum was isolated from scales of the nose. Both women liked gardening and M. gypseum was isolated from the garden soil of these women by a hair-baiting technique. The first case had a cat, a mouse and an owl, and the second had a dog. Hairbrush culture of these pets, however, was negative. So we concluded both cases were infected with M. gypseum from garden soil. We isolated M. gypseum from soil collected in Chigasaki city. Of the 7 fungal cultures from 10 samples, 2 cultures were identified as M. gypseum.

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