47 results on '"Mai Tsuchiya"'
Search Results
2. [A case of ataxic gait disturbance due to 1-bromopropane neurotoxicity]
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Yuto Morishima, Toko Fukao, Mai Tsuchiya, Takanori Hata, Kazumasa Shindo, and Yoshihisa Takiyama
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Neurology (clinical) - Abstract
A 55-year-old man presented a slowly progressive sensory disorder, predominantly in both lower limbs, and gait disturbance. Neurological examinations revealed abnormal sensation and spasticity in both lower limbs, and a wide-based gait. Although examination revealed mild hyperchloremia and decreased motor conduction velocity in the peroneal nerve, head and whole spine MRI, and spinal fluid examination were normal. His job history revealed he had been engaged in metal cleaning work using 1-bromopropane (1-BP) for three years. His serum bromide concentration was increased to 175.6 mg/l (standard value: 5 or less), so we diagnosed him as having 1-BP neurotoxicity. The serum bromide concentration decreased after avoidance of exposure to 1-BP, but the gait disturbance remained. It was considered that we should obtain a detailed job history and measure the serum bromide concentration in patients with a sensory disorder in the extremities and gait disturbance of unknown origin.
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- 2022
3. Sympathetic nerve outflow to skin in a case with dentatorubral-pallidoluysian atrophy
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Mai Tsuchiya, Tohko Sato, Yoshihisa Takiyama, Kishin Koh, Kazumasa Shindo, Takafumi Kurita, Takanori Hata, Takahiro Natori, Takamura Nagasaka, and Akane Satake
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medicine.medical_specialty ,Neural Conduction ,Sympathetic nerve ,Mental arithmetic ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Cerebellum ,Skin Physiological Phenomena ,Physiology (medical) ,Internal medicine ,Reflex ,medicine ,Humans ,Skin ,Subclinical infection ,Dentatorubral-pallidoluysian atrophy ,business.industry ,General Medicine ,Middle Aged ,Myoclonic Epilepsies, Progressive ,medicine.disease ,Electric Stimulation ,Neurology ,030220 oncology & carcinogenesis ,Spinocerebellar ataxia ,Cardiology ,Female ,Surgery ,Neurology (clinical) ,Reflex latency ,Adrenergic Fibers ,business ,030217 neurology & neurosurgery - Abstract
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by slowly progressive cerebellar ataxia. Previously, autonomic symptoms or dysfunction have not been reported. To evaluate subclinical autonomic dysfunction regarding thermoregulatory function in SCA, we recorded sympathetic outflow to skin in a DRPLA patient confirmed by genetic analysis. We recorded skin sympathetic nerve activity (SSNA), which was elicited and recorded by using the microneurographical technique. In results, the resting frequency of SSNA bursts was very low (8.2 ± 0.4 bursts/min [institutional normal range: 20.8 ± 2.4 bursts/min]). However, acceleration of SSNA bursts induced by mental arithmetic stress was confirmed. The amplitude of reflex bursts induced by electrical stimuli was slightly low (9.6 ± 1.6 μV [institutional normal range: 10.9 ± 2.2 μV]), and the reflex latency was mildly prolonged (872 ± 23.7 msec [institutional normal range: 761.9 ± 51.7 msec]). These results suggest potentially central autonomic dysfunction in this patient with DRPLA. To our knowledge, this is the first report to record SSNA and confirm subclinical autonomic dysfunction in a case with DRPLA.
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- 2021
4. A patient with recurrent multiloculated hydrocephalus after Cryptococcal ventriculitis
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Yoshihisa Takiyama, Takahiro Natori, Mai Tsuchiya, Hiroyuki Kinouchi, Ryusuke Takaki, and Mitsuto Hanihara
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Male ,medicine.medical_specialty ,Urinary system ,Amnesia ,Meningitis, Cryptococcal ,Cerebral Ventriculitis ,Lateral ventricles ,Neoplasms ,medicine ,Ventriculitis ,Humans ,Confusion ,business.industry ,Gait Disturbance ,Middle Aged ,Myelitis ,medicine.disease ,Hydrocephalus ,Surgery ,Shunt (medical) ,medicine.anatomical_structure ,Ventricle ,Encephalitis ,Neurology (clinical) ,medicine.symptom ,business - Abstract
We report here a rare case of adult-onset multiloculated hydrocephalus (MLH) after Cryptococcal meningitis. A 63-year-old man had Cryptococcal ventriculitis in 2011, and he recovered with treatment of antimycotic drugs. However, he was admitted again because of disorientation and amnesia, and brain MRI showed dilation of the inferior horn of the left lateral ventricle. He underwent a ventriculoperitoneal shunt (VPS) for noncommunicating hydrocephalus in 2019, and the disorientation and amnesia improved. One year after the VPS, he was admitted because of urinary dysfunction and gait disturbance. Brain MRI showed dilation of the bilateral anterior horns of the lateral ventricles. He underwent an additional VPS into the space in 2020, and urinary dysfunction and gait disturbance improved. This case was supposed that the symptom in agreement with the dilated ventricle by MLH was shown.
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- 2021
5. Chédiak–Higashi syndrome presenting as a hereditary spastic paraplegia
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Hiroyuki Ishiura, Makio Takahashi, Shoji Tsuji, Mai Tsuchiya, Takeshi Nakamura, Kohei Suzuyama, Hideo Hara, Haruo Shimazaki, Yoshihisa Takiyama, and Kishin Koh
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integumentary system ,Cerebellar ataxia ,business.industry ,Hereditary spastic paraplegia ,Chédiak–Higashi syndrome ,medicine.disease ,Oculocutaneous albinism ,nervous system diseases ,hemic and lymphatic diseases ,Immunology ,Genetics ,Spastic ,Primary immunodeficiency ,Medicine ,Spasticity ,medicine.symptom ,business ,Paraplegia ,Genetics (clinical) - Abstract
Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by weakness and leg spasticity. LYST is responsible for Chediak-Higashi syndrome (CHS), which exhibits partial oculocutaneous albinism, primary immunodeficiency, and bleeding tendency in childhood. Although neurological symptoms of CHS also appear in adulthood, a phenotype of spastic paraplegia has rarely been reported in CHS. In this study, we investigated LYST mutations in 387 HSP patients through the Japan Spastic Paraplegia Research Consortium to clarify the frequency of LYST mutations in HSP, finding six adult patients with LYST mutations in four HSP families. They exhibited intellectual disability, cerebellar ataxia, neuropathy, and pyramidal signs. Meanwhile, only 15 patients with CHS in childhood have been revealed in a decade by a nationwide survey in Japan. Thus, LYST mutations might indicate a HSP phenotype in a considerable number of adult patients with CHS.
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- 2021
6. Age‐related changes in blood pressure and heart rates of patients with Parkinson's disease
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Takafumi Kurita, Mai Tsuchiya, Yuta Ichinose, Kazumasa Shindo, Yuto Morishima, Yoshihisa Takiyama, Yumi Suwa, Takamura Nagasaka, Takanori Hata, Kishin Koh, Toko Fukao, and Akane Satake
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medicine.medical_specialty ,Parkinson's disease ,business.industry ,Endocrinology, Diabetes and Metabolism ,Medical record ,Disease duration ,Disease ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Blood pressure ,Internal medicine ,Age related ,Internal Medicine ,Cardiology ,Medicine ,cardiovascular diseases ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,circulatory and respiratory physiology - Abstract
This study evaluated yearly changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rates (HR) for patients with Parkinson's disease (PD). Data were collected for the last 10 years from medical records of 28 PD patients and 30 non-PD patients with other neurological disorders. Age-related changes in each group were analyzed by year using mean values of SBP, DBP, and HR obtained at their bi-monthly visits. In results, PD patients had a gradual decrease in SBP with longer disease duration, and mean SBP significantly decreased from Year 7-11 compared to the mean values for Year 1 (p < .001 or p < .01). In non-PD patients, mean SBP significantly increased from Year 4-11 compared to the mean values for Year 1 (p < .001 or p < .01). This is the first study to report age-related changes of BP in individual patients with PD over 10 years.
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- 2020
7. RFC1 repeat expansion in Japanese patients with late-onset cerebellar ataxia
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Yuta Ichinose, Yoshihisa Takiyama, Andrea Cortese, Mai Tsuchiya, Keisuke Shimozono, Toshihisa Ohtsuka, Yeon-Jeong Kim, Kishin Koh, Haitian Nan, Takanori Hata, and Lihua Gao
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0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Vestibular areflexia ,Ataxia ,Cerebellar ataxia ,business.industry ,Sleep apnea ,Disease ,030105 genetics & heredity ,medicine.disease ,RFC1 ,03 medical and health sciences ,030104 developmental biology ,Genetics ,medicine ,medicine.symptom ,business ,Trinucleotide repeat expansion ,Genetics (clinical) ,Cohort study - Abstract
Recently, the expansion of an intronic AAGGG repeat in the replication factor C subunit 1 (RFC1) gene was reported to cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In Europeans, the expansion accounted for 22% of sporadic patients with late-onset ataxia. We genotyped 37 Japanese patients comprising 25 familial (autosomal recessive or undecided transmission) and 12 sporadic ones with late-onset ataxia. We found intronic repeat expansions in RFC1 in three (12%) of the familial patients and one (8.5%) of the sporadic ones. Although our cohort study was small, the disease frequency in Japanese patients with CANVAS might be lower than that in European ones. In addition, we found biallelic ACAGG repeat expansion in one patient, indicating ACAGG repeat expansion might cause CANVAS. Clinically, we found one patient with sleep apnea syndrome, which has not been reported previously. Thus, this study might expand the clinical and genetic spectrum of CANVAS.
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- 2020
8. A Novel Heterozygous Missense Variant in the CIAO1 Gene in a Family with Alzheimer's Disease: The Val67Ile Variant Promotes the Interaction of CIAO1 and Amyloid-β Protein Precursor
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Mai Tsuchiya, Yeon-Jeong Kim, Yoshihisa Takiyama, Takeshi Ikeuchi, Norikazu Hara, Toko Fukao, Kenya Nishioka, Toshihisa Ohtsuka, Nobutaka Hattori, Noriko Hara, Haitian Nan, and Atsushi Hagihara
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Male ,amyloid-β protein precursor processing ,Heterozygote ,Amyloid β ,Short Communication ,Mutation, Missense ,Neurogenetics ,Neuroimaging ,Disease ,Biology ,Amyloid beta-Protein Precursor ,Japan ,Alzheimer Disease ,medicine ,CIAO1 protein ,Dementia ,Missense mutation ,Humans ,Genetic Predisposition to Disease ,Cognitive decline ,Protein precursor ,neurogenetics ,Gene ,Aged ,Genetics ,General Neuroscience ,Brain ,familial ,General Medicine ,medicine.disease ,cognitive decline ,Metallochaperones ,Psychiatry and Mental health ,Clinical Psychology ,CIAO1 ,Female ,Geriatrics and Gerontology ,Alzheimer’s disease ,dementia - Abstract
Familial dementia is a rare inherited disease involving progressive impairment of memory, thinking, and behavior. We report a novel heterozygous pathogenic variant (c.199G > A, p.Val67Ile) in the CIAO1 gene that appears to be co-segregated with Alzheimer’s disease in a Japanese family. Biochemical analysis of CIAO1 protein revealed that the variant increases the interaction of CIAO1 with immature amyloid-β protein precursor (AβPP), but not mature or soluble AβPP, indicating plausible CIAO1 involvement in AβPP processing. Our study indicates that a heterozygous variant in the CIAO1 gene may be closely related to autosomal dominant familial dementia.
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- 2021
9. Chédiak-Higashi syndrome presenting as a hereditary spastic paraplegia
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Kishin, Koh, Mai, Tsuchiya, Hiroyuki, Ishiura, Haruo, Shimazaki, Takeshi, Nakamura, Hideo, Hara, Kohei, Suzuyama, Makio, Takahashi, Shoji, Tsuji, and Yoshihisa, Takiyama
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Adult ,Family Health ,Male ,Spastic Paraplegia, Hereditary ,Vesicular Transport Proteins ,Middle Aged ,Pedigree ,Diagnosis, Differential ,Phenotype ,Mutation ,Exome Sequencing ,Humans ,Female ,Chediak-Higashi Syndrome - Abstract
Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by weakness and leg spasticity. LYST is responsible for Chédiak-Higashi syndrome (CHS), which exhibits partial oculocutaneous albinism, primary immunodeficiency, and bleeding tendency in childhood. Although neurological symptoms of CHS also appear in adulthood, a phenotype of spastic paraplegia has rarely been reported in CHS. In this study, we investigated LYST mutations in 387 HSP patients through the Japan Spastic Paraplegia Research Consortium to clarify the frequency of LYST mutations in HSP, finding six adult patients with LYST mutations in four HSP families. They exhibited intellectual disability, cerebellar ataxia, neuropathy, and pyramidal signs. Meanwhile, only 15 patients with CHS in childhood have been revealed in a decade by a nationwide survey in Japan. Thus, LYST mutations might indicate a HSP phenotype in a considerable number of adult patients with CHS.
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- 2021
10. Novel
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Haitian, Nan, Yeon-Jeong, Kim, Mai, Tsuchiya, Aki, Ishida, Hirotaka, Haro, Masaki, Hiraide, Toshihisa, Ohtsuka, and Yoshihisa, Takiyama
- Abstract
Variations inWe present a Japanese family with a novelThe missense variation (c.265TC, p.Trp89Arg) inThis study might have revealed an example of a monogenic origin of atypical parkinsonism in females with
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- 2021
11. Paraneoplastic sensorimotor neuropathy associated with mediastinal germ cell tumor: favorable outcome after high-dose intravenous immunoglobulin therapy
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Yoshihisa Takiyama, Mai Tsuchiya, Kazumasa Shindo, Takamura Nagasaka, and Kishin Koh
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Pathology ,medicine.medical_specialty ,Neurology ,Mediastinal germ cell tumor ,biology ,business.industry ,High dose intravenous immunoglobulin ,Dermatology ,General Medicine ,medicine.disease ,Psychiatry and Mental health ,Paraneoplastic sensorimotor neuropathy ,biology.protein ,Medicine ,Neurology (clinical) ,Neurosurgery ,Favorable outcome ,Antibody ,business ,Neuroradiology - Published
- 2019
12. Exome Sequencing Reveals a Novel Homozygous Frameshift Mutation in the CYP7B1 Gene in a Japanese Patient with SPG5
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Masaki Hiraide, Keisuke Shimozono, Yuta Ichinose, Mai Tsuchiya, Yoshihisa Takiyama, Kishin Koh, and Haitian Nan
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Genetics ,CYP7B1 ,Hereditary spastic paraplegia ,business.industry ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Hyperintensity ,Frameshift mutation ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Mutation (genetic algorithm) ,Internal Medicine ,medicine ,030211 gastroenterology & hepatology ,business ,Gene ,Exome sequencing - Abstract
SPG5 is a rare subtype of autosomal recessive hereditary spastic paraplegia caused by a homozygous mutation in the oxysterol 7α-hydroxylase gene, CYP7B1. We describe the first Japanese patient with SPG5 with a novel mutation in the CYP7B1 gene. On exome sequencing, we identified a homozygous frameshift mutation, c.741delA, p.K247fs, in exon 3 of the CYP7B1 gene. The patient showed spastic paraparesis with white matter hyperintensities in the bilateral corona radiata and periventricular and subcortical regions on brain magnetic resonance imaging. The present study expands the mutation spectrum of CYP7B1 and provides an opportunity to study the genotype-phenotype correlation in SPG5.
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- 2019
13. Non-convulsive status epilepticus associated with neuronal intranuclear inclusion disease: A case report and literature review
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Yoshihisa Takiyama, Takanori Hata, Mai Tsuchiya, Takamura Nagasaka, Kishin Koh, Kazumasa Shindo, Yuta Ichinose, Gen Sobue, and Jun Sone
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Nausea ,Status epilepticus ,Neuronal intranuclear inclusion disease ,Electroencephalography ,Article ,lcsh:RC321-571 ,Leukoencephalopathy ,03 medical and health sciences ,Behavioral Neuroscience ,NEURONAL INTRANUCLEAR INCLUSION DISEASE ,Autonomic neuropathy ,0302 clinical medicine ,medicine ,Skin biopsy ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Cerebral atrophy ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Hyperintensity ,030104 developmental biology ,Generalized periodic discharges ,Neurology ,Non-convulsive status epilepticus ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
We report a case of neuronal intranuclear inclusion disease (NIID) confirmed by detection of intranuclear inclusions in a skin biopsy specimen. Brain magnetic resonance imaging showed mild cerebral atrophy and linear hyperintensities at the corticomedullary junction on diffusion-weighted images. This patient developed nonconvulsive status epilepticus with generalized periodic discharges on electroencephalography after recurrent symptoms of paroxysmal nausea and slowly progressive cognitive decline. There have been no previous reports of NIID with nonconvulsive status epilepticus to our knowledge. Since adult patients with NIID display a wide variety of clinical manifestations, skin biopsy should be considered in patients who have leukoencephalopathy of unknown origin., Highlights • We report a case of neuronal intranuclear inclusion disease (NIID) confirmed by detection of intranuclear inclusions in a skin biopsy specimen. • This patient developed non-convulsive status epilepticus with generalized periodic discharge on electroencephalography. • Since adult patients with neuronal NIID display a wide variety of clinical manifestations, skin biopsy should be recommended in patients who have leukoencephalopathy of unknown origin.
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- 2019
14. Novel GARS mutation presenting as autosomal dominant intermediate Charcot‐Marie‐Tooth disease
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Yoshihisa Takiyama, Ryusuke Takaki, Takanori Hata, Yuta Ichinose, Kishin Koh, Haitian Nan, and Mai Tsuchiya
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Genetics ,Proband ,congenital, hereditary, and neonatal diseases and abnormalities ,Nerve biopsy ,medicine.diagnostic_test ,General Neuroscience ,Sural nerve biopsy ,Biology ,Hand weakness ,nervous system diseases ,03 medical and health sciences ,Tooth disease ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Mutation (genetic algorithm) ,medicine ,Missense mutation ,Neurology (clinical) ,030217 neurology & neurosurgery ,Exome sequencing - Abstract
We report the first family with a glycyl-tRNA synthetase (GARS) mutation with autosomal dominant intermediate Charcot-Marie-Tooth disease (DI-CMT). The proband and the proband's father presented with gait disturbance and hand weakness. Both patients displayed moderately decreased conduction velocities (MNCV) (ranging from 29.2 to 37.8 m/s). A sural nerve biopsy of the father revealed evidence of both axonal loss and demyelination. On exome sequencing, in both the proband and his father, we identified a novel missense mutation (c.643G > C, p.Asp215His) in the GARS gene in a heterozygous state, which is considered to be pathogenic for this DI-CMT family. The present study broadens current knowledge about intermediate CMT and the phenotypic spectrum of defects associated with GARS.
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- 2018
15. Novel SLC9A6 Variation in Female Carriers With Intellectual Disability and Atypical Parkinsonism
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Haitian Nan, Yeon-Jeong Kim, Mai Tsuchiya, Aki Ishida, Hirotaka Haro, Masaki Hiraide, Toshihisa Ohtsuka, and Yoshihisa Takiyama
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Neurology (clinical) ,Genetics (clinical) - Abstract
Background and ObjectivesVariations in SLC9A6 cause the X-linked neurologic disorder Christianson syndrome in males. Meanwhile, female carriers with SLC9A6 variations may remain asymptomatic or develop intellectual disability, behavioral problems, and psychiatric illnesses. Only a few female carriers have been reported to have associated atypical parkinsonism in late life.MethodsWe present a Japanese family with a novel SLC9A6 variation identified by quad whole-exome sequencing analysis and a reverse phenotyping strategy. The molecular and cellular impacts of the W89R variation in vitro were examined.ResultsThe missense variation (c.265T>C, p.Trp89Arg) in SLC9A6 cosegregated with atypical parkinsonism and intellectual disability in female carriers of this family. The female carriers in this family presented with bradykinesia, rigidity, and tremor, predominately on the right side. We found that the W89R variation changed membrane traffic of NHE6-harboring vesicles, indicating potential involvement in the disease pathogenesis.DiscussionThis study might have revealed an example of a monogenic origin of atypical parkinsonism in females with SLC9A6 variations and draw attention to this understudied female-specific phenotype in clinical practice.
- Published
- 2022
16. RFC1 repeat expansion in Japanese patients with late-onset cerebellar ataxia
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Mai, Tsuchiya, Haitian, Nan, Kishin, Koh, Yuta, Ichinose, Lihua, Gao, Keisuke, Shimozono, Takanori, Hata, Yeon-Jeong, Kim, Toshihisa, Ohtsuka, Andrea, Cortese, and Yoshihisa, Takiyama
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Aged, 80 and over ,Male ,DNA Repeat Expansion ,Japan ,Humans ,Female ,Genetic Predisposition to Disease ,Middle Aged ,Replication Protein C ,Introns ,Aged ,Spinocerebellar Degenerations - Abstract
Recently, the expansion of an intronic AAGGG repeat in the replication factor C subunit 1 (RFC1) gene was reported to cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In Europeans, the expansion accounted for 22% of sporadic patients with late-onset ataxia. We genotyped 37 Japanese patients comprising 25 familial (autosomal recessive or undecided transmission) and 12 sporadic ones with late-onset ataxia. We found intronic repeat expansions in RFC1 in three (12%) of the familial patients and one (8.5%) of the sporadic ones. Although our cohort study was small, the disease frequency in Japanese patients with CANVAS might be lower than that in European ones. In addition, we found biallelic ACAGG repeat expansion in one patient, indicating ACAGG repeat expansion might cause CANVAS. Clinically, we found one patient with sleep apnea syndrome, which has not been reported previously. Thus, this study might expand the clinical and genetic spectrum of CANVAS.
- Published
- 2020
17. A case of local tetanus presenting spastic paraplegia mimicking myelitis
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Kazumasa Shindo, Mai Tsuchiya, Fumikazu Kobayashi, Yoshihisa Takiyama, Takamura Nagasaka, and Nobuo Yamashiro
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Adult ,Male ,Opisthotonus ,Myelitis ,Hyperreflexia ,Trismus ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Tetanus Toxoid ,medicine ,Spastic ,Humans ,030212 general & internal medicine ,Spasticity ,Paraplegia ,Tetanus ,business.industry ,medicine.disease ,Magnetic Resonance Imaging ,Treatment Outcome ,Spinal Cord ,Anesthesia ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
A 35-year-old male was admitted to our hospital because of suspected myelitis. T2-weighted spinal MRI revealed a high intensity area at Th7-9. On admission, he showed mild weakness of the lower extremities and hyperreflexia of all extremities. Therefore, he was diagnosed with having spastic paraplegia. He presented no trismus or opisthotonos. There was pleocytosis in the cerebral spinal fluid. Dysuria, constipation and spasticity of the bilateral legs worsened, even though we administered methylprednisolone pulse therapy. Nonetheless, the symptoms had progressed on the 11th hospital day, opisthotonus and optic hyperesthesia were presented. On the 13th hospital day, we suspected local tetanus and administered tetanus toxoid. After one month, his symptoms had gradually improved. In the case of spastic paraplegia showing a subacute progression course and a faint abnormality on spinal MRI, the possibility of local tetanus should be considered.
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- 2018
18. A Japanese family with a novel nonsense mutation in the spastin gene associated with both cerebellar ataxia and cognitive impairment
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Yoshihisa Takiyama, Kazumasa Shindo, Aki Ishida, Mai Tsuchiya, Kishin Koh, and Yuta Ichinose
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Genetics ,Cerebellar ataxia ,business.industry ,media_common.quotation_subject ,Nonsense mutation ,Nonsense ,Spastin ,Neurology ,DNA Mutational Analysis ,medicine ,Neurology (clinical) ,medicine.symptom ,Cognitive impairment ,business ,Gene ,media_common - Published
- 2019
19. Decreasing 123I-ioflupane SPECT accumulation and 123I-MIBG myocardial scintigraphy uptake in a patient with a novel homozygous mutation in the ZFYVE26 gene
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Yoshihisa Takiyama, Kazumasa Shindo, Mai Tsuchiya, Kishin Koh, and Takamura Nagasaka
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0301 basic medicine ,medicine.medical_specialty ,Pathology ,Neurology ,business.industry ,Dermatology ,General Medicine ,03 medical and health sciences ,Psychiatry and Mental health ,030104 developmental biology ,0302 clinical medicine ,Text mining ,Myocardial scintigraphy ,Mutation (genetic algorithm) ,medicine ,Neurology (clinical) ,Neurosurgery ,business ,Gene ,030217 neurology & neurosurgery ,Neuroradiology - Published
- 2018
20. Clinicopathological features of adult-onset neuronal intranuclear inclusion disease
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Naoko Uehara, Yutaka Suto, Satoshi Yokoi, Gen Sobue, Naoyuki Kitagawa, Haruki Koike, Takuya Konno, Mai Tsuchiya, Akihiro Hashiguchi, Hiroshi Sugiyama, Hiroyuki Nakayasu, Kunihiko Araki, Yoshihisa Takiyama, Makoto Takahashi, Ryu Katsumata, Toshiyasu Kato, Jun Sone, Shinnosuke Takagi, Yutaka Kohno, Yasushi Iwasaki, Michi Kawamoto, Norito Kokubun, Takashi Kurashige, Keiko Mori, Hiroshi Takashima, Tomohiko Nakamura, Mari Yoshida, Masaru Kuriyama, Masahisa Katsuno, Fumiaki Tanaka, Hajime Yoshimura, and Tomonori Inagaki
- Subjects
Adult ,Male ,0301 basic medicine ,leukoencephalopathy ,Pathology ,medicine.medical_specialty ,Ataxia ,Adolescent ,intranuclear inclusion ,Intranuclear Inclusion Bodies ,Leukoencephalopathy ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Eosinophilic ,medicine ,Humans ,Dementia ,Age of Onset ,skin biopsy ,Hyaline ,Aged ,Muscle Weakness ,medicine.diagnostic_test ,business.industry ,Muscle weakness ,Neurodegenerative Diseases ,Original Articles ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,diffusion-weighted image ,Pedigree ,030104 developmental biology ,Skin biopsy ,Female ,Neurology (clinical) ,medicine.symptom ,Differential diagnosis ,business ,030217 neurology & neurosurgery - Abstract
Neuronal intranuclear inclusion disease (NIID) has highly variable clinical manifestations. Sone et al. describe the clinical and pathological features of 57 adult-onset cases diagnosed by postmortem dissection/antemortem skin biopsy. They report ‘dementia dominant’ and ‘limb weakness’ subtypes, and recommend consideration of NIID in the differential diagnosis of leukoencephalopathy and neuropathy., Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated ‘dementia dominant group’, followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated ‘limb weakness group’, followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and familial NIID cases presented with a decline in Mini-Mental State Examination and Frontal Assessment Battery scores. Based on these clinicopathological features, we proposed a diagnosis flow chart of adult-onset NIID. Our study suggested that the prevalence rate of adult-onset NIID may be higher than previously thought, and that NIID may be underdiagnosed. We should take NIID into account for differential diagnosis of leukoencephalopathy and neuropathy.
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- 2016
21. Novel SLC20A2 mutation in primary familial brain calcification with disturbance of sustained phonation and orofacial apraxia
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Kishin Koh, Haitian Nan, Kazumasa Shindo, Yoshihisa Takiyama, Mai Tsuchiya, Ryusuke Takaki, Shuji Hanyu, and Yuta Ichinose
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Disturbance (geology) ,Orofacial apraxia ,business.industry ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Mutation (genetic algorithm) ,medicine ,Neurology (clinical) ,Phonation ,business ,030217 neurology & neurosurgery ,Calcification - Published
- 2018
22. Sympathetic neurograms showing characteristics of both muscle and skin sympathetic nerve activity in a case with pure autonomic failure
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Akane Satake, Mai Tsuchiya, Kazumasa Shindo, Yuta Ichinose, Takamura Nagasaka, Takanori Hata, Toko Sato, Yoshihisa Takiyama, Kishin Koh, and Naofumi Kurita
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medicine.medical_specialty ,Neurology ,Endocrine and Autonomic Systems ,business.industry ,05 social sciences ,Sympathetic nerve activity ,medicine.disease ,050105 experimental psychology ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,medicine ,Cardiology ,0501 psychology and cognitive sciences ,Neurology (clinical) ,Reflex latency ,business ,Pure autonomic failure ,030217 neurology & neurosurgery - Published
- 2018
23. Sympathetic outflow to skin predicts central autonomic dysfunction in multiple system atrophy
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Kazumasa Shindo, Yoshihisa Takiyama, Takamura Nagasaka, Naofumi Kurita, Akane Satake, Takanori Hata, Mai Tsuchiya, Toko Fukao, Yuta Ichinose, and Kishin Koh
- Subjects
medicine.medical_specialty ,Neurology ,Sympathetic Nervous System ,Stimulation ,Dermatology ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Internal medicine ,Reflex ,medicine ,Humans ,030212 general & internal medicine ,Skin ,Vasomotor ,Skin blood flow ,business.industry ,General Medicine ,Multiple System Atrophy ,medicine.disease ,Electric Stimulation ,Psychiatry and Mental health ,Cardiology ,Neurology (clinical) ,Reflex latency ,Sympathetic outflow ,business ,030217 neurology & neurosurgery - Abstract
To find out the physiological method for evaluating the severity of central autonomic dysfunction, we performed detailed evaluation of cutaneous vasomotor neural function in a comparatively large sample of multiple system atrophy (MSA). We evaluated cutaneous vasomotor neural function in 24 MSA patients. Skin sympathetic nerve activity (SSNA) and sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex [SVR]) were recorded at rest, as well as reflex changes after electrical stimulation. The parameters investigated were SSNA frequency at rest, reflex latency and amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and spontaneous SVR and SSR frequency. There were negative correlations between resting SSNA and disease duration or the SCOPA-AUT score, but these were not significant. SSNA reflex latency displayed significant positive correlations with disease duration and SCOPA-AUT score (p
- Published
- 2019
24. Pathological findings in a patient with non-dystrophic myotonia with a mutation of the SCN4A gene; a case report
- Author
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Yuta Ichinose, Takamura Nagasaka, Yoshihisa Takiyama, Mai Tsuchiya, Kishin Koh, Takanori Hata, Haitian Nan, and Kazumasa Shindo
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Heterozygote ,Myotonic dystrophy ,Case Report ,lcsh:RC346-429 ,Myotonia ,03 medical and health sciences ,0302 clinical medicine ,Biopsy ,medicine ,Humans ,030212 general & internal medicine ,NAV1.4 Voltage-Gated Sodium Channel ,Muscle, Skeletal ,lcsh:Neurology. Diseases of the nervous system ,Non-dystrophic myotonia ,Aged ,CLCN1 ,Muscle biopsy ,medicine.diagnostic_test ,biology ,business.industry ,Skeletal muscle ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,Mutation ,biology.protein ,Neurology (clinical) ,Percussion myotonia ,medicine.symptom ,business ,SCN4A ,030217 neurology & neurosurgery ,Muscle contraction - Abstract
Background Non-dystrophic myotonias (NDMs) are skeletal muscle disorders involving myotonia distinct from myotonic dystrophy. It has been reported that the muscle pathology is usually normal or comprises mild myopathic changes in NDMs. We describe various pathological findings mimicking those of myotonic dystrophy (DM) in biopsied muscle specimens from a patient with NDMs with a long disease duration. Case presentation A 66-year-old Japanease man presented eye closure myotonia, percussion myotonia and grip myotonia together with the warm-up phenomenon and cold aggravation from early childhood. On genetic analysis, a heterozygous mutation of the SCN4A gene (c.2065 C > T, p.L689F), with no mutation of the CLCN1, DMPK, or ZNF9/CNBP gene, was detected. He was diagnosed as having NDMs. A biopsy of the biceps brachii muscle showed increasing fiber size variation, internal nuclei, chained nuclei, necrotic fibers, fiber splitting, endomysial fibrosis, pyknotic nuclear clumps and disorganized intermyofibrillar networks. Sarcoplasmic masses, tubular aggregates and ragged-red fibers were absent. Conclusion It is noteworthy that the present study revealed various pathological findings resembling those seen in DM, although the pathology is usually normal or mild in NDMs. The pathological similarities may be due to muscular modification with long-standing myotonia or excessive muscle contraction based on abnormal channel activity. Electronic supplementary material The online version of this article (10.1186/s12883-019-1360-0) contains supplementary material, which is available to authorized users.
- Published
- 2019
25. Exome Sequencing Reveals a Novel Homozygous Frameshift Mutation in the CYP7B1 Gene in a Japanese Patient with SPG5
- Author
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Haitian, Nan, Keisuke, Shimozono, Yuta, Ichinose, Mai, Tsuchiya, Kishin, Koh, Masaki, Hiraide, and Yoshihisa, Takiyama
- Subjects
CYP7B1 ,frameshift mutation ,Spastic Paraplegia, Hereditary ,white matter lesions ,Homozygote ,Cytochrome P450 Family 7 ,Brain ,Case Report ,Exons ,SPG5 ,Magnetic Resonance Imaging ,Steroid Hydroxylases ,Exome Sequencing ,Disease Progression ,Humans ,Exome ,Female ,hereditary spastic paraplegia ,Aged - Abstract
SPG5 is a rare subtype of autosomal recessive hereditary spastic paraplegia caused by a homozygous mutation in the oxysterol 7α-hydroxylase gene, CYP7B1. We describe the first Japanese patient with SPG5 with a novel mutation in the CYP7B1 gene. On exome sequencing, we identified a homozygous frameshift mutation, c.741delA, p.K247fs, in exon 3 of the CYP7B1 gene. The patient showed spastic paraparesis with white matter hyperintensities in the bilateral corona radiata and periventricular and subcortical regions on brain magnetic resonance imaging. The present study expands the mutation spectrum of CYP7B1 and provides an opportunity to study the genotype-phenotype correlation in SPG5.
- Published
- 2018
26. Neuroimaging, genetic, and enzymatic study in a Japanese family with a GBA gross deletion
- Author
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Yoshihisa Takiyama, Shinichi Morishita, Jun Yoshimura, Takako Umeda, Shoji Tsuji, Masaki Tanaka, Kazumasa Shindo, Jun Mitsui, Mai Tsuchiya, Koichiro Doi, Kishin Koh, Yuta Ichinose, Hiroyuki Ishiura, Jun Goto, Hajime Yamauchi, Hiroshi Onishi, Nobuo Yamashiro, and Toshihisa Ohtsuka
- Subjects
0301 basic medicine ,Male ,Parkinson's disease ,Neuroimaging ,Disease ,medicine.disease_cause ,Pathogenesis ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Asian People ,Japan ,Leukocytes ,Medicine ,Humans ,Family ,Gene ,Aged ,Genetics ,Aged, 80 and over ,Tomography, Emission-Computed, Single-Photon ,Mutation ,business.industry ,Dementia with Lewy bodies ,Reverse Transcriptase Polymerase Chain Reaction ,Brain ,Parkinson Disease ,Exons ,Middle Aged ,medicine.disease ,Iofetamine ,Pedigree ,030104 developmental biology ,Neurology ,Glucosylceramidase ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,Radiopharmaceuticals ,business ,Glucocerebrosidase ,030217 neurology & neurosurgery ,Gene Deletion ,Tropanes - Abstract
Introduction Glucocerebrosidase gene (GBA) variants are associated with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The molecular mechanisms underlying these diseases with GBA variants, however, are not well understood. In order to determine the effect of a deletion mutation in GBA, we performed a neuroimaging, genetic, and enzymatic study in a Japanese family with a gross deletion of exons 3 to 11 in GBA. Methods We performed [123I] FP-CIT SPECT and [123I] N-isopropyl-p-iodoamphetamine SPECT (IMP-SPECT), and determined GBA expression and glucocerebrosidase (GCase) activity in leukocytes in two GBA-associated PD patients and nine unaffected individuals (including four mutation carriers) in a Japanese family with a heterozygous gross deletion mutation in the GBA gene. Results The two PD patients and two of the four clinically unaffected carriers showed decreased [123I] FP-CIT uptake. IMP-SPECT showed a pattern like that in DLB in one patient. When we compared PD patients with GBA mutations with clinically unaffected carriers, there was a poor correlation between the development of PD and the expression level of GBA or GCase activity. Conclusion We confirmed the gross deletion mutation in the GBA gene, which appeared to be associated with the PD or reduced [123I] FP-CIT in this family. However, since we cannot conclude whether a reduction of GCase activity is directly correlated with the pathogenesis of PD or not, longitudinal follow-up of this family is needed.
- Published
- 2018
27. [An Autopsy Case of Meningoencephalitis and Cerebral Infarction that Developed with Ramsay Hunt Syndrome and Disseminated Herpes Zoster]
- Author
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Nobuo, Yamashiro, Takamura, Nagasaka, Naoki, Ooishi, Mai, Tsuchiya, Ryusuke, Takaki, Fumikazu, Kobayashi, Kazumasa, Shindo, and Yoshihisa, Takiyama
- Subjects
Aged, 80 and over ,Male ,Myoclonic Cerebellar Dyssynergia ,Fatal Outcome ,Meningoencephalitis ,Humans ,Autopsy ,Cerebral Infarction ,Herpes Zoster - Abstract
We report here the clinical presentation and subsequent autopsy of a 90-year-old man who developed small papules with pain and swelling in his right ear. On admission, he exhibited right facial nerve paralysis, neck stiffness and Kernig's sign. The cell count was elevated and the varicella-zoster virus-PCR was positive in the CSF. Brain magnetic resonance imaging showed hyperintense lesions in the left pons and left temporal lobe, in FLAIR images. We diagnosed the patient with Ramsay Hunt syndrome and meningoencephalitis due to varicella-zoster virus. Although the symptoms of meningitis improved following treatment with intravenous acyclovir (750 mg/day initially, raised to 1,125 mg/day), 16 days after admission, he died suddenly due to gastrointestinal hemorrhage. The autopsy findings included lymphocytic infiltration of the leptomeninges and perivascular space of the cerebrum, and slight parenchyma in the left temporal lobe and insula, as the main histological features. Encephalitis due to varicella zoster virus has been recognized as a vasculopathy affecting large and small vessels. Pathological confirmation is rare in varicella zoster virus meningoencephalitis.
- Published
- 2018
28. Ubiquitin ligase CHIP suppresses cancer stem cell properties in a population of breast cancer cells
- Author
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Yuka Nakajima, Tamaki Morishita, Mai Tsuchiya, Naoya Hirata, Keiji Kimura, Yasunari Kanda, and Hiroyuki Kishimoto
- Subjects
Ubiquitin-Protein Ligases ,Population ,Biophysics ,Breast Neoplasms ,Biochemistry ,law.invention ,Breast cancer ,Ubiquitin ,Cancer stem cell ,law ,medicine ,Humans ,education ,Molecular Biology ,Cell Proliferation ,education.field_of_study ,biology ,Cancer ,Cell Differentiation ,Cell Biology ,medicine.disease ,Ubiquitin ligase ,Immunology ,MCF-7 Cells ,Neoplastic Stem Cells ,biology.protein ,Cancer research ,Suppressor ,Female ,Stem cell - Abstract
Cancer stem cells (CSCs) have several distinctive characteristics, including high metastatic potential, tumor-initiating potential, and properties that resemble normal stem cells such as self-renewal, differentiation, and drug efflux. Because of these characteristics, CSC is regarded to be responsible for cancer progression and patient prognosis. In our previous study, we showed that a ubiquitin E3 ligase carboxyl terminus of Hsc70-interacting protein (CHIP) suppressed breast cancer malignancy. Moreover, a recent clinical study reported that CHIP expression levels were associated with favorable prognostic parameters of patients with breast cancer. Here we show that CHIP suppresses CSC properties in a population of breast cancer cells. CHIP depletion resulted in an increased proportion of CSCs among breast cancers when using several assays to assess CSC properties. From our results, we propose that inhibition of CSC properties may be one of the functions of CHIP as a suppressor of cancer progression.
- Published
- 2014
29. A case of Bickerstaff brainstem encephalitis with transient reflex myoclonus
- Author
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Ryusuke Takaki, Kishin Kho, Yumi Suwa, Yoshihisa Takiyama, Takamura Nagasaka, and Mai Tsuchiya
- Subjects
Adult ,Myoclonus ,congenital, hereditary, and neonatal diseases and abnormalities ,Weakness ,Time Factors ,Bickerstaff brainstem encephalitis ,digestive system ,Methylprednisolone ,03 medical and health sciences ,Dysarthria ,0302 clinical medicine ,Gangliosides ,mental disorders ,Medicine ,Humans ,Mycoplasma Infections ,Autoantibodies ,business.industry ,Myography ,Immunoglobulins, Intravenous ,medicine.disease ,Dysphagia ,nervous system diseases ,Pulse Therapy, Drug ,030220 oncology & carcinogenesis ,Anesthesia ,Reflex ,Encephalitis ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Jaw jerk reflex ,medicine.drug ,Brain Stem - Abstract
A 33-year-old woman was admitted due to disturbance of consciousness, dysarthria, dysphagia, sensory disturbances and weakness of the left upper limb after mycoplasma infection. She was treated with intravenous immunoglobulin and intravenous high-dose methylprednisolone as Bickerstaff brainstem encephalitis (BBE). On the 15th hospital day, reflex myoclonus appeared on her face, neck, body and limbs induced by techniques of jaw jerk reflex and patellar tendon reflex. The myoclonus was disappeared after two weeks in accordance with improvement of BBE. The transient reflex myoclonus may be originated from brainstem lesion which was affected by BBE. Reflex myoclonus is thought to be rare symptom in patient with BBE.
- Published
- 2017
30. Pre- and postganglionic vasomotor dysfunction causes distal limb coldness in multiple system atrophy
- Author
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Kishin Koh, Takanori Hata, Mai Tsuchiya, Fumikazu Kobayashi, Yuta Ichinose, Yoshihisa Takiyama, Kazumasa Shindo, Takamura Nagasaka, and Nobuo Yamashiro
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Autonomic Fibers, Preganglionic ,Stimulation ,Multiple system atrophy (MSA) ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Sympathetic Fibers, Postganglionic ,Internal medicine ,Reflex ,Laser-Doppler Flowmetry ,Medicine ,Humans ,Vascular Diseases ,Aged ,Skin ,integumentary system ,Vasomotor ,business.industry ,Anatomy ,Laser Doppler velocimetry ,Middle Aged ,Multiple System Atrophy ,medicine.disease ,Electric Stimulation ,Peripheral ,030104 developmental biology ,Neurology ,Vasoconstriction ,Cardiology ,Autonomic Fibers, Postganglionic ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Blood Flow Velocity - Abstract
The detailed pathophysiology of limb coldness in multiple system atrophy (MSA) is unknown.We evaluated cutaneous vasomotor neural function in 18 MSA patients with or without limb coldness, and in 20 healthy volunteers as controls. We measured resting skin sympathetic nerve activity (SSNA) and spontaneous changes of the sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex: SVR), as well as SVR and reflex changes of SSNA after electrical stimulation. The parameters investigated were the SSNA frequency at rest, amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and skin blood flow velocity.Both the resting frequency of SSNA and the amplitude of SSNA reflex bursts were significantly lower in the MSA group than the control group (p0.001 and p0.05, respectively). There were no significant differences between the two groups with regard to the absolute decrease or percent reduction of SVR volume. The recovery time showed no significant difference between all MSA patients and control groups, but it was significantly prolonged in six MSA patients with limb coldness compared with that in the control group and that in MSA patients without limb coldness (p0.01). The skin blood flow velocity was significantly slower in the MSA group than in the control group (p0.001).In MSA patients, limb coldness might occur due to impairments of the peripheral circulation based on prolongation of vasoconstriction and a decrease of skin blood flow velocity secondary to combined pre- and postganglionic skin vasomotor dysfunction.
- Published
- 2017
31. Skin vasomotor regulation in patients with multiple system atrophy
- Author
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Nobuyuki Kurita, Mai Tsuchiya, Fumikazu Kobayashi, Kazumasa Shindo, T. Sato, Yuta Ichinose, Kishin Koh, Nobuo Yamashiro, Yoshihisa Takiyama, Takanori Hata, Takamura Nagasaka, and A. Satake
- Subjects
medicine.medical_specialty ,Atrophy ,Neurology ,Vasomotor ,business.industry ,Internal medicine ,Cardiology ,medicine ,In patient ,Neurology (clinical) ,medicine.disease ,business - Published
- 2017
32. Vasomotor regulation in patients with multiple system atrophy
- Author
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Yoshihisa Takiyama, Takanori Hata, Takamura Nagasaka, Kazumasa Shindo, Kishin Koh, Mai Tsuchiya, Fumikazu Kobayashi, Nobuo Yamashiro, and Yuta Ichinose
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Neurology ,Sympathetic Nervous System ,Rest ,Blood Pressure ,03 medical and health sciences ,Orthostatic vital signs ,Electrocardiography ,Hypotension, Orthostatic ,0302 clinical medicine ,Atrophy ,stomatognathic system ,Heart Rate ,parasitic diseases ,mental disorders ,Heart rate ,medicine ,Humans ,In patient ,Biological Psychiatry ,Aged ,Aged, 80 and over ,Vasomotor ,business.industry ,Muscles ,Healthy subjects ,Blood Pressure Determination ,Middle Aged ,Multiple System Atrophy ,medicine.disease ,nervous system diseases ,Psychiatry and Mental health ,030104 developmental biology ,Blood pressure ,nervous system ,Anesthesia ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
To investigate the vasomotor regulation in multiple system atrophy (MSA), we simultaneously recorded muscle sympathetic nerve activity (MSNA), heart rate, and blood pressure in 14 MSA patients without syncope and 18 healthy subjects. Resting MSNA bursts were significantly less frequent in MSA patients than healthy subjects (p
- Published
- 2016
33. Changes in sympathetic thermoregulatory function with aging
- Author
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Yoshihisa Takiyama, Kazumasa Shindo, Mai Tsuchiya, Takamura Nagasaka, Fumikazu Kobayashi, and Nobuo Yamashiro
- Subjects
Adult ,Male ,medicine.medical_specialty ,Aging ,Neurology ,Sympathetic Nervous System ,Stimulation ,Sympathetic skin response ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,030502 gerontology ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,Endocrine and Autonomic Systems ,business.industry ,Sympathetic nerve activity ,virus diseases ,food and beverages ,Galvanic Skin Response ,Thermoregulation ,Middle Aged ,digestive system diseases ,Electric Stimulation ,Vasomotor System ,Endocrinology ,Female ,Neurology (clinical) ,Reflex latency ,0305 other medical science ,business ,030217 neurology & neurosurgery ,Body Temperature Regulation - Abstract
We recorded skin sympathetic nerve activity (SSNA), SSR, and SVR in 30 subjects. SSNA and SVR showed a slight decrease and spontaneous changes in resting SSR were significantly less frequent in older subjects compared with younger subjects (p
- Published
- 2016
34. [A Case of Acute Limbic Encephalitis with Sjögren's Syndrome]
- Author
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Hiroyuki, Shinmura, Takamura, Nagasaka, Mai, Tsuchiya, Akiko, Onohara, Ryusuke, Takaki, and Yoshihisa, Takiyama
- Subjects
Sjogren's Syndrome ,Limbic Encephalitis ,Acute Disease ,Humans ,Female ,Middle Aged ,Hippocampus ,Magnetic Resonance Imaging ,Temporal Lobe - Abstract
A 52-year-old woman developed abnormal behavior and disturbance of consciousness subsequent to several days with a cold. On admission, she was very confused, with incoherent speech, and an inability to recognize family faces. Diffusion weighted MRI showed high intensity signal change in the bilateral medial temporal lobes, including the hippocampus. Cerebrospinal fluid examination was normal. Tests including various viral antibody titers provided no evidence of infection. Several neuronal antibodies including anti-VGKC and -NMDA receptor antibody were absent. Evidence of malignancy was not apparent. She was diagnosed with acute limbic encephalitis complicated by Sjögren's syndrome (SjS), due to the fact that she had a past history of SjS, elevation of anti-SS-A antibody, pleuritis and pericarditis. Her symptoms gradually improved after administration of steroids including pulse therapy; however, her amnesia remained for a long time. In diagnosing acute limbic encephalitis, we should consider SjS as an underlying disease, even though it is rare.
- Published
- 2016
35. Huge Brain Cystic Lesions Resulting from Metronidazole-Induced Encephalopathy
- Author
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Kazaumasa Shindo, Ryusuke Takaki, Mai Tsuchiya, Takamura Nagasaka, Yoshihisa Takiyama, Kishin Koh, and Shinji Togashi
- Subjects
Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,Cerebellar ataxia ,business.industry ,Encephalopathy ,Neurological examination ,Corpus callosum ,medicine.disease ,Apraxia ,White matter ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Agraphia ,Medicine ,030212 general & internal medicine ,medicine.symptom ,business ,Abscess ,030217 neurology & neurosurgery - Abstract
Metronidazole-induced encephalopathy (MIE) is a rare clinical condition resulting from long-term use of metronidazole. The symptoms and brain MRI changes in MIE usually resolve dramatically on discontinuation of treatment, and thus MIE with brain cystic lesions has rarely been reported. A 49-year-old woman was treated for a lumbar abscess with oral administration of 1.5 g/day of metronidazole for 4 months. Neurological examination revealed aphasia, apraxia, agraphia, cerebellar ataxia, and cognitive impairment. On brain MRI, diffusion-weighted imaging and the apparent diffusion coefficients were consistent with cytotoxic edema in the corpus callosum and subcortical white matter, representing delayed huge cystic lesions. Thus, we should be aware of MIE with irreversible brain lesions.
- Published
- 2016
36. Estrogen and antiestrogens alter breast cancer invasiveness by modulating the transforming growth factor-β signaling pathway
- Author
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Hiromi Hiyoshi, Ichiaki Ito, Natsuka Goto, Yuka Nakajima, Mai Tsuchiya, and Junn Yanagisawa
- Subjects
Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Estrogen receptor ,Breast Neoplasms ,Smad Proteins ,Biology ,Metastasis ,Cell Movement ,Transforming Growth Factor beta ,Cell Line, Tumor ,Internal medicine ,medicine ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,skin and connective tissue diseases ,Estrogen receptor beta ,Estrogen Antagonists ,Estrogen Receptor alpha ,Cancer ,Estrogens ,General Medicine ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Endocrinology ,Oncology ,Estrogen ,Tumor progression ,Estrogen receptor alpha ,hormones, hormone substitutes, and hormone antagonists ,Tamoxifen ,Signal Transduction ,medicine.drug - Abstract
In the later stages of breast cancer, estrogen receptor (ER)α-negative cancers typically have higher histological grades than ERα-positive cancers, and transforming growth factor (TGF)-β promotes invasion and metastasis. Our previous study indicated that ERα inhibited TGF-β signaling by inducing the degradation of Smad in an estrogen-dependent manner. In the present study, we report that the suppressive effects of ERα and estrogen on tumor progression are mediated by inhibiting TGF-β signaling. Furthermore, we investigated the effects of antiestrogens such as ICI182,780 (ICI) or tamoxifen (TAM) on TGF-β signaling and breast cancer invasiveness. The levels of total Smad and pSmad were reduced by estrogen, whereas ICI slightly increased them, and TAM had no effect. To investigate the effect of antiestrogens on breast cancer invasiveness, we generated highly migratory and invasive MCF-7-M5 cells. The migration and invasion of these cells were suppressed by the inhibitor of TGF-β receptor kinase, SB-505124, and estrogen. However, antiestrogens did not suppress the migration and invasion of these cells. In addition, we screened TGF-β target genes whose expression was reduced by estrogen treatment and identified four genes associated with breast cancer invasiveness and poor prognosis. The expression of these genes was not decreased by antiestrogens. These observations provide a new insight into estrogen function and the mechanisms underlying estrogen-mediated suppression of tumor progression. (Cancer Sci 2011; 102: 1501–1508)
- Published
- 2011
37. The Lighting Design for The Administration Building of Seibo Jogakuin(<Special Issue>Japanese Illumination Designs Highly Recognized in Overseas as Well 2010)
- Author
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Mai Tsuchiya and Osamu Tomita
- Subjects
Architectural engineering ,Business ,Electrical and Electronic Engineering ,Administration (government) - Published
- 2011
38. Morphological features of mitochondria in anti-mitochondrial antibodies-positive myositis
- Author
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Yoshihisa Takiyama, Kazumasa Shindo, K. Kho, Takamura Nagasaka, Yuta Ichinose, Mai Tsuchiya, Takanori Hata, Ryusuke Takaki, and Nobuo Yamashiro
- Subjects
Pathology ,medicine.medical_specialty ,Neurology ,medicine ,biology.protein ,Neurology (clinical) ,Biology ,Mitochondrion ,Antibody ,medicine.disease ,Myositis - Published
- 2017
39. Dopamine transporter imaging and glucocerebrosidase activity in parkinson’s disease patients with a heterozygous gross deletion mutation in gba in a japanese family
- Author
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Shoji Tsuji, Yoshihisa Takiyama, Yuta Ichinose, Jun Goto, Takamura Nagasaka, H. Onishi, Mai Tsuchiya, Nobuo Yamashiro, Toshihisa Ohtsuka, Y. Omiya, Jun Mitsui, Kishin Koh, Hiroyuki Ishiura, Hajime Yamauchi, Takako Umeda, S. Kazumasa, and Masaaki Tanaka
- Subjects
medicine.medical_specialty ,Parkinson's disease ,biology ,business.industry ,medicine.disease ,Glucocerebrosidase activity ,Endocrinology ,Neurology ,Internal medicine ,Deletion mutation ,biology.protein ,Medicine ,Neurology (clinical) ,business ,Dopamine transporter - Published
- 2017
40. No relation between sympathetic outflow to muscles and respiratory function in amyotrophic lateral sclerosis
- Author
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Ryusuke Takaki, Akiko Onohara, Mai Tsuchiya, Kishin Koh, Fumikazu Kobayashi, Nobuo Yamashiro, Yoshihisa Takiyama, Megumi Fukumoto, Kazumasa Shindo, Takamura Nagasaka, and Yuta Ichinose
- Subjects
Adult ,Male ,Vital capacity ,medicine.medical_specialty ,Sympathetic nervous system ,Sympathetic Nervous System ,Blood Pressure ,Heart Rate ,Internal medicine ,Heart rate ,medicine ,Humans ,Respiratory function ,Amyotrophic lateral sclerosis ,Muscle, Skeletal ,Aged ,business.industry ,Respiration ,Amyotrophic Lateral Sclerosis ,Microneurography ,Anatomy ,Middle Aged ,medicine.disease ,Autonomic nervous system ,medicine.anatomical_structure ,Blood pressure ,Neurology ,Autonomic Nervous System Diseases ,Cardiology ,Female ,Neurology (clinical) ,Blood Gas Analysis ,business - Abstract
In amyotrophic lateral sclerosis (ALS), not only impairment of motor neurons but also impairment of the autonomic nervous system has been demonstrated by previous physiological studies. Several investigators have reported a correlation between autonomic dysfunction and respiratory dysfunction in ALS. This study analyzed the relation between parameters of respiratory function and muscle sympathetic nerve activity (MSNA) in a large number of ALS patients.In 50 patients with ALS (mean age (SD): 62.1 (11.7) years), MSNA, heart rate (HR), and blood pressure (BP) were recorded simultaneously. The arterial oxygen content (PaO2), arterial carbon dioxide content (PaCO2), and forced vital capacity expressed as a percentage of the predicted value for healthy controls (%VC) were determined as parameters of respiratory function.There were no significant correlations between MSNA and PaO2, PaCO2, %VC, or the disability score. Analysis of chronological changes in 14 patients examined twice showed that the disability score and PaCO2 were significantly increased, and %VC was significantly more decreased at the second examination compared with the first examination (p0.01 and p0.05, respectively). In contrast, HR, BP, burst rate of MSNA, and age-adjusted MSNA exhibited no significant changes between the first and second examinations.These findings show that gradual deterioration of respiratory function in ALS patients is not associated with changes of quantitative MSNA parameters, which may suggest that abnormality of the autonomic nervous system is a primary feature of ALS.
- Published
- 2015
41. Perturbation of ribosome biogenesis drives cells into senescence through 5S RNP-mediated p53 activation
- Author
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Ryohei Furumai, Takao Kuroda, Natsuka Goto, Mai Tsuchiya, Naohiro Katagiri, Junn Yanagisawa, Kazuho Nishimura, Takuya Kumazawa, Keiji Kimura, and Akiko Murayama
- Subjects
Senescence ,Ribosomal Proteins ,Transcriptional Activation ,Nucleolus ,Ribosome biogenesis ,RNA-binding protein ,Cell Cycle Proteins ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Downregulation and upregulation ,Animals ,Humans ,RNA, Small Interfering ,RRNA processing ,lcsh:QH301-705.5 ,Cells, Cultured ,Cellular Senescence ,Ribonucleoprotein particle ,RNA, Ribosomal, 5S ,Nuclear Proteins ,RNA-Binding Proteins ,Proto-Oncogene Proteins c-mdm2 ,RRNA transcription ,Cell biology ,Up-Regulation ,lcsh:Biology (General) ,MCF-7 Cells ,RNA Interference ,Tumor Suppressor Protein p53 ,Ribosomes ,Cell Nucleolus - Abstract
SummaryThe 5S ribonucleoprotein particle (RNP) complex, consisting of RPL11, RPL5, and 5S rRNA, is implicated in p53 regulation under ribotoxic stress. Here, we show that the 5S RNP contributes to p53 activation and promotes cellular senescence in response to oncogenic or replicative stress. Oncogenic stress accelerates rRNA transcription and replicative stress delays rRNA processing, resulting in RPL11 and RPL5 accumulation in the ribosome-free fraction, where they bind MDM2. Experimental upregulation of rRNA transcription or downregulation of rRNA processing, mimicking the nucleolus under oncogenic or replicative stress, respectively, also induces RPL11-mediated p53 activation and cellular senescence. We demonstrate that exogenous expression of certain rRNA-processing factors rescues the processing defect, attenuates p53 accumulation, and increases replicative lifespan. To summarize, the nucleolar-5S RNP-p53 pathway functions as a senescence inducer in response to oncogenic and replicative stresses.
- Published
- 2014
42. CHIP buffers heterogeneous Bcl-2 expression levels to prevent augmentation of anticancer drug-resistant cell population
- Author
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Hiromi Hiyoshi, Yuki Hayashi, Hiroyuki Kishimoto, T Morishita, Yuka Nakajima, Mai Tsuchiya, Ryohei Furumai, Junn Yanagisawa, Tsuyoshi Waku, and Keiji Kimura
- Subjects
Cancer Research ,Ubiquitin-Protein Ligases ,Population ,Antineoplastic Agents ,Breast Neoplasms ,Breast cancer ,Genetic variation ,Gene expression ,Genetics ,medicine ,Humans ,education ,Molecular Biology ,Gene ,Gene knockdown ,education.field_of_study ,biology ,Cancer ,medicine.disease ,Molecular biology ,Ubiquitin ligase ,Proto-Oncogene Proteins c-bcl-2 ,Drug Resistance, Neoplasm ,Gene Knockdown Techniques ,biology.protein ,Cancer research ,MCF-7 Cells ,Female ,Cisplatin - Abstract
Many types of cancer display heterogeneity in various features, including gene expression and malignant potential. This heterogeneity is associated with drug resistance and cancer progression. Recent studies have shown that the expression of a major protein quality control ubiquitin ligase, carboxyl terminus of Hsc70-interacting protein (CHIP), is negatively correlated with breast cancer clinicopathological stages and poor overall survival. Here we show that CHIP acts as a capacitor of heterogeneous Bcl-2 expression levels and prevents an increase in the anticancer drug-resistant population in breast cancer cells. CHIP knockdown in breast cancer cells increased variation in Bcl-2 expression levels, an antiapoptotic protein, among the cells. Our results also showed that CHIP knockdown increased the proportion of anticancer drug-resistant cells. These findings suggest that CHIP buffers variation in gene expression levels, affecting resistance to anticancer drugs. In single-cell clones derived from breast cancer cell lines, CHIP knockdown did not alter the variation in Bcl-2 expression levels and the proportion of anticancer drug-resistant cells. In contrast, when clonal cells were treated with a mutagen, the variation in Bcl-2 expression levels and proportion of anticancer drug-resistant cells were altered by CHIP knockdown. These results suggest that CHIP masks genetic variations to suppress heterogeneous Bcl-2 expression levels and prevents augmentation of the anticancer drug-resistant population of breast cancer cells. Because genetic variation is a major driver of heterogeneity, our results suggest that the degree of heterogeneity in expression levels is decided by a balance between genetic variation and the buffering capacity of CHIP.
- Published
- 2014
43. Lung toxicity assessment using bronchoalveolar lavage fluid and pleural lavage fluid cytology by intratracheal treatment in rats
- Author
-
Maki Makita, Masato Naya, Mai Tsuchiya, Ryota Tanaka, Hiroshi Takehara, and Makoto Hayashi
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Pulmonary toxicity ,Buffers ,Sodium Chloride ,Toxicology ,Ether ,Rats, Sprague-Dawley ,Chlorides ,Cytology ,Toxicity Tests ,Lavage fluid ,Medicine ,Animals ,Anesthesia ,Lung ,Pleural Cavity ,medicine.diagnostic_test ,Isoflurane ,business.industry ,Water ,respiratory system ,Pleural cavity ,respiratory tract diseases ,Rats ,Specific Pathogen-Free Organisms ,Trachea ,Bronchoalveolar lavage ,medicine.anatomical_structure ,Instillation, Drug ,Zinc Compounds ,Toxicity ,business ,Bronchoalveolar Lavage Fluid ,medicine.drug - Abstract
Usefulness of bronchoalveolar lavage fluid (BALF) and pleural cavity lavage fluid (PLF) as an experimental material was evaluated for the assessment of pulmonary toxicity of chemicals in rats. From the viewpoint of safety, isoflurane can be used for euthanasia/anesthesia because there was no difference in biological properties of BALF between diethyl ether and isoflurane. Here, we also recognized phosphate buffered saline (PBS) and distilled water equally as a solvent/vehicle for negative control. PLF is also provided as a useful target material as well as BALF for assessing chemical lung toxicity. To evaluate the method, we used zinc chloride as a model chemical and obtained the expected and satisfied results. We may conclude that the intratracheal treatment and combination usage of BALF and PLF as a target material is a good method for assessment of chemical pulmonary (lung and plural cavity) toxicity in rats.
- Published
- 2014
44. Novel Nucleolar Pathway Connecting Intracellular Energy Status with p53 Activation*
- Author
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Takuya Kumazawa, Akiko Murayama, Yuka Nakajima, Takao Kuroda, Hiroshi Masumoto, Mai Tsuchiya, Chie Yamaguchi, Naohiro Katagiri, Kazuho Nishimura, Wakana Ono, Keiji Kimura, and Junn Yanagisawa
- Subjects
Nucleocytoplasmic Transport Proteins ,Cell cycle checkpoint ,Nucleolus ,Apoptosis ,P300-CBP Transcription Factors ,Biology ,Biochemistry ,Cell Line, Tumor ,Humans ,p300-CBP Transcription Factors ,Molecular Biology ,Nucleoplasm ,RNA ,Nuclear Proteins ,RNA-Binding Proteins ,Acetylation ,Cell Biology ,Cell cycle ,RRNA transcription ,Cell biology ,DNA-Binding Proteins ,Multiprotein Complexes ,Tumor Suppressor Protein p53 ,Energy Metabolism ,Intracellular ,Cell Nucleolus ,Transcription Factors - Abstract
In response to a shortage of intracellular energy, mammalian cells reduce energy consumption and induce cell cycle arrest, both of which contribute to cell survival. Here we report that a novel nucleolar pathway involving the energy-dependent nucleolar silencing complex (eNoSC) and Myb-binding protein 1a (MYBBP1A) is implicated in these processes. Namely, in response to glucose starvation, eNoSC suppresses rRNA transcription, which results in a reduction in nucleolar RNA content. As a consequence, MYBBP1A, which is anchored to the nucleolus via RNA, translocates from the nucleolus to the nucleoplasm. The translocated MYBBP1A induces acetylation and accumulation of p53 by enhancing the interaction between p300 and p53, which eventually leads to the cell cycle arrest (or apoptosis). Taken together, our results indicate that the nucleolus works as a sensor that transduces the intracellular energy status into the cell cycle machinery.
- Published
- 2011
45. 2-(4-Hydroxy-3-methoxyphenyl)-benzothiazole suppresses tumor progression and metastatic potential of breast cancer cells by inducing ubiquitin ligase CHIP
- Author
-
Junn Yanagisawa, Yasunari Kanda, Mai Tsuchiya, Yuka Nakajima, Keisuke Iida, Naoya Hirata, Natsuka Goto, Hiromi Hiyoshi, and Kazuo Nagasawa
- Subjects
Lung Neoplasms ,Ubiquitin-Protein Ligases ,Mice, Nude ,Antineoplastic Agents ,Triple Negative Breast Neoplasms ,Adenocarcinoma ,Stem cell marker ,Article ,Breast cancer ,Cancer stem cell ,Cell Line, Tumor ,Spheroids, Cellular ,medicine ,Animals ,Humans ,Benzothiazoles ,RNA, Small Interfering ,Mice, Inbred BALB C ,Multidisciplinary ,biology ,Cell growth ,Guaiacol ,medicine.disease ,Aryl hydrocarbon receptor ,Molecular biology ,Xenograft Model Antitumor Assays ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,Receptors, Aryl Hydrocarbon ,Tumor progression ,biology.protein ,Cancer research ,Female ,Signal Transduction - Abstract
Breast cancer is the most common malignancy among women and has poor survival and high recurrence rates for aggressive metastatic disease. Notably, triple-negative breast cancer (TNBC) is a highly aggressive cancer and there is no preferred agent for TNBC therapy. In this study, we show that a novel agent, 2-(4-hydroxy-3-methoxyphenyl)-benzothiazole (YL-109), has ability to inhibit breast cancer cell growth and invasiveness in vitro and in vivo. In addition, YL-109 repressed the sphere-forming ability and the expression of stem cell markers in MDA-MB-231 mammosphere cultures. YL-109 increased the expression of carboxyl terminus of Hsp70-interacting protein (CHIP), which suppresses tumorigenic and metastatic potential of breast cancer cells by inhibiting the oncogenic pathway. YL-109 induced CHIP transcription because of the recruitment of the aryl hydrocarbon receptor (AhR) to upstream of CHIP gene in MDA-MB-231 cells. Consistently, the antitumor effects of YL-109 were depressed by CHIP or AhR knockdown in MDA-MB-231 cells. Taken together, our findings indicate that a novel agent YL-109 inhibits cell growth and metastatic potential by inducing CHIP expression through AhR signaling and reduces cancer stem cell properties in MDA-MB-231 cells. It suggests that YL-109 is a potential candidate for breast cancer therapy.
- Published
- 2014
46. Identification and Evaluation of Potentially Genotoxic Agricultural and Food-related Chemicals
- Author
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Jin Tanaka, Motoko Takahashi, Atsuko Horibe, Masamitsu Honma, Mai Tsuchiya, Takeshi Morita, and Makoto Hayashi
- Subjects
business.industry ,Agriculture ,Environmental engineering ,Environmental science ,Identification (biology) ,business ,Biotechnology - Published
- 2013
47. The E3 Ubiquitin Ligase Activity of Trip12 Is Essential for Mouse Embryogenesis
- Author
-
Natsuka Goto, Yuka Nakajima, Satoru Takahashi, Yoh-ichi Kawabe, Yuki Hayashi, Naoya Iwasaki, Tatsuya Watanabe, Ryohei Furumai, Masashi Kajiro, Masatsugu Ema, Hiroyuki Kishimoto, Akiko Murayama, Mai Tsuchiya, Miyuki Katano, Hisashi Oishi, and Junn Yanagisawa
- Subjects
Male ,Chromosomal Proteins, Non-Histone ,Ubiquitin-Protein Ligases ,Cellular differentiation ,lcsh:Medicine ,Embryonic Development ,medicine.disease_cause ,Biochemistry ,Chromatin remodeling ,Mice ,Ubiquitin ,Gene expression ,Genetics ,medicine ,Animals ,lcsh:Science ,Biology ,Cyclin-Dependent Kinase Inhibitor p16 ,Embryonic Stem Cells ,Mutation ,Multidisciplinary ,biology ,Protein Stability ,lcsh:R ,Cell Cycle ,Proteins ,Cell cycle ,Embryo, Mammalian ,Molecular biology ,Chromatin ,Protein ubiquitination ,Protein Structure, Tertiary ,Ubiquitin ligase ,Cell biology ,Phenotype ,biology.protein ,lcsh:Q ,Epigenetics ,Female ,Gene Function ,Transcriptome ,Animal Genetics ,Research Article - Abstract
Protein ubiquitination is a post-translational protein modification that regulates many biological conditions [1], [2], [3], [4]. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1 [5], [6]. However, the significance of Trip12 in vivo is largely unknown. Here we show that the ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis. A homozygous mutation in Trip12 (Trip12mt/mt) that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12mt/mt embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16 [7], [8], [9], [10]. In contrast, Trip12mt/mt ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12mt/mt ES cells had increased levels of the BAF57 protein (a component of the SWI/SNF chromatin remodeling complex) and altered gene expression patterns. These data suggest that Trip12 is involved in global gene expression and plays an important role in mouse development.
- Published
- 2011
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