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1.
Commun Biol ; 7(1): 413, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594382

RESUMO

Better understanding of the earliest molecular pathologies of all neurodegenerative diseases is expected to improve human therapeutics. We investigated the earliest molecular pathology of spinocerebellar ataxia type 1 (SCA1), a rare familial neurodegenerative disease that primarily induces death and dysfunction of cerebellum Purkinje cells. Extensive prior studies have identified involvement of transcription or RNA-splicing factors in the molecular pathology of SCA1. However, the regulatory network of SCA1 pathology, especially central regulators of the earliest developmental stages and inflammatory events, remains incompletely understood. Here, we elucidated the earliest developmental pathology of SCA1 using originally developed dynamic molecular network analyses of sequentially acquired RNA-seq data during differentiation of SCA1 patient-derived induced pluripotent stem cells (iPSCs) to Purkinje cells. Dynamic molecular network analysis implicated histone genes and cytokine-relevant immune response genes at the earliest stages of development, and revealed relevance of ISG15 to the following degradation and accumulation of mutant ataxin-1 in Purkinje cells of SCA1 model mice and human patients.


Assuntos
Células-Tronco Pluripotentes Induzidas , Ataxias Espinocerebelares , Animais , Humanos , Camundongos , Citocinas , Células-Tronco Pluripotentes Induzidas/patologia , Camundongos Transgênicos , Células de Purkinje/fisiologia , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/patologia , Ubiquitinas
2.
Toxicon ; 230: 107161, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37201801

RESUMO

Ciguatera fish poisoning (CFP) is a foodborne illness affecting > 50,000 people worldwide annually. It is caused by eating marine invertebrates and fish that have accumulated ciguatoxins (CTXs). Recently, the risk of CFP to human health, the local economy, and fishery resources have increased; therefore, detection methods are urgently needed. Functional assays for detecting ciguatoxins in fish include receptor binding (RBA) and neuroblastoma cell-based assay (N2a assay), which can detect all CTX congeners. In this study, we made these assays easier to use. For RBA, an assay was developed using a novel near-infrared fluorescent ligand, PREX710-BTX, to save valuable CTXs. In the N2a assay, a 1-day assay was developed with the same detection performance as the conventional 2-day assay. Additionally, in these assays, we used calibrated CTX standards from the Pacific determined by quantitative NMR for the first time to compare the relative potency of congeners, which differed significantly among previous studies. In the RBA, there was almost no difference in the binding affinity among congeners, showing that the differences in side chains, stereochemistry, and backbone structure of CTXs did not affect the binding affinity. However, this result did not correlate with the toxic equivalency factors (TEFs) based on acute toxicity in mice. In contrast, the N2a assay showed a good correlation with TEFs based on acute toxicity in mice, except for CTX3C. These findings, obtained with calibrated toxin standards, provide important insights into evaluating the total toxicity of CTXs using functional assays.


Assuntos
Ciguatera , Ciguatoxinas , Neuroblastoma , Camundongos , Humanos , Animais , Ciguatoxinas/toxicidade , Ligação Proteica , Peixes
3.
Eur J Neurol ; 30(7): 1861-1870, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36943150

RESUMO

BACKGROUND AND PURPOSE: Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is an adult-onset leukoencephalopathy caused by mutations in CSF1R. The present study aimed to explore the broader genetic spectrum of CSF1R-related leukoencephalopathy in association with clinical and imaging features. METHODS: Mutational analysis of CSF1R was performed for 100 consecutive patients with adult-onset leukoencephalopathy. Sequence and copy number variation (CNV) analyses of CSF1R were performed. The genomic ranges of the deletions were determined by long-read sequencing. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing the CSF1R mutants identified in this study. RESULTS: CSF1R mutations were identified in 15 patients, accounting for 15% of the adult-onset leukoencephalopathy cases. Seven novel and five previously reported CSF1R mutations were identified. The novel mutations, including three missense and one in-frame 3 bp deletion, were located in the tyrosine kinase domain (TKD) of CSF1R. Functional assays revealed that none of the novel mutations in the TKD showed autophosphorylation of CSF1R. Two partial deletions of CSF1R were identified that resulted in lack of the C-terminal region, including the distal TKD, in two patients. Various clinical features including cognitive impairment, psychiatric symptoms and gait disturbance were observed. Various degrees of the white matter lesions and corpus callosum abnormalities on magnetic resonance imaging and characteristic calcifications on computed tomography were observed as imaging features. CONCLUSIONS: Our results highlight the importance of examining the CNV of CSF1R even when Sanger or exome sequencing reveals no CSF1R mutations. Genetic examination of sequences and CNV analyses of CSF1R are recommended for an accurate diagnosis of CSF1R-related leukoencephalopathy.


Assuntos
Leucoencefalopatias , Mutação de Sentido Incorreto , Receptores de Fator Estimulador de Colônias , Adulto , Humanos , Variações do Número de Cópias de DNA , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Leucoencefalopatias/patologia , Mutação , Receptores de Fator Estimulador de Colônias/genética
4.
Cerebellum ; 22(6): 1308-1311, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36227410

RESUMO

Early-onset ataxias are often difficult to diagnose due to the genetic and phenotypic heterogeneity of patients. Whole exome sequencing (WES) is a powerful method for determining causative mutations of early-onset ataxias. We report a case in which a novel de novo KIF1A mutation was identified in a patient with ataxia, intellectual disability and mild foot deformity.A patient presented with sporadic forms of ataxia with mild foot deformity, intellectual disability, peripheral neuropathy, pyramidal signs, and orthostatic hypotension. WES was used to identify a novel de novo mutation in KIF1A, a known causative gene of neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment syndrome (NESCAVS).We report a novel phenotype of NESCAVS that is associated with a novel de novo missense mutation in KIF1A, which provides valuable information for the diagnosis of NESCAVS even in the era of WES. Early rehabilitation of patients with NESCAVS may prevent symptom worsening and improve the disease course.


Assuntos
Ataxia Cerebelar , Doenças Cerebelares , Deformidades do Pé , Deficiência Intelectual , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Ataxia Cerebelar/genética , Mutação/genética , Mutação de Sentido Incorreto , Fenótipo , Cinesinas/genética
7.
Neuromuscul Disord ; 32(6): 516-520, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35527200

RESUMO

Myoglobinopathy is a rare autosomal dominant myopathy that manifests in adulthood with proximal and axial weakness and variable respiratory and cardiac failure. Muscle pathology features associated with myoglobinopathy include characteristic sarcoplasmic bodies in skeletal and cardiac muscles. Here we present the first case of myoglobinopathy in an Asian individual. Although myoglobinopathy patients were reported not to have facial muscle weakness, our patient had orbicularis oculi muscle weakness, tongue weakness and atrophy, poor movement of the soft palate, and dysarthria. This is also the first reported case of tube feeding in a patient with myoglobinopathy. The patient started NPPV 18 years after onset, indicating that an older age of onset may have resulted in slow disease progression. Muscle selectivity, characteristic muscle pathology, and progressive cardiopulmonary dysfunction and dysphagia are hallmarks of this disease.


Assuntos
Debilidade Muscular , Doenças Musculares , Adulto , Disartria , Músculos Faciais , Humanos , Debilidade Muscular/diagnóstico , Debilidade Muscular/etiologia , Debilidade Muscular/patologia , Músculo Esquelético/patologia , Doenças Musculares/patologia
8.
Nutrients ; 12(10)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066591

RESUMO

Although folate deficiency was reported to be associated with hyperhomocysteinemia, influence of folate supplementation on cognition remains controversial. Therefore, we explored the effects of folate supplementation on the cognition and Homocysteine (Hcy) level in relatively short periods in patients with folate deficiency and cognitive impairment. Enrolled 45 patients (mean age of 79.7 ± 7.9 years old) with folate deficiency (<3.6 ng/mL) with cognitive impairment underwent Mini-Mental State Examination (MMSE), and laboratory examinations, including folate, vitamin B12, and Hcy. The degree of hippocampal atrophy in MRI was estimated using a voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Patients were administrated folate (5 mg/day), then Hcy, and MMSE score were re-examined after 28 to 63 days. Mean Hcy significantly decreased from 25.0 ± 18.0 to 11.0 ± 4.3 nmol/mL (p < 0.001). Average MMSE scores also significantly changed from 20.1 ± 4.7 to 22.2 ± 4.3 (p < 0.001). The degree of change in the MMSE score and basic Hcy or Hcy change was significantly positively correlated, while degree of hippocampal atrophy in MRI did not. Although several factors should be taken into account, folate supplementation ameliorated cognitive impairment, at least for a short period, in patients with folate deficiency.


Assuntos
Cognição , Disfunção Cognitiva/sangue , Disfunção Cognitiva/psicologia , Suplementos Nutricionais , Deficiência de Ácido Fólico/psicologia , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Homocisteína/sangue , Idoso , Idoso de 80 Anos ou mais , Atrofia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/tratamento farmacológico , Feminino , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/dietoterapia , Hipocampo/patologia , Humanos , Masculino , Testes de Estado Mental e Demência , Fatores de Tempo , Resultado do Tratamento
9.
Transplant Proc ; 52(6): 1880-1883, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32620392

RESUMO

Warm ischemia and reperfusion injury (IRI) is a prognostic factor in donation after cardiac death donor transplantation. However, a reliable method to predict IRI before transplantation has not been established. The aim of this study was to identify predictive markers of hepatic IRI by simultaneous measurement of endogenous molecules using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Rats were subjected to hepatic warm ischemia (70%) for 30 or 90 minutes and subsequent reperfusion. The livers were collected at the end of ischemia and 1 hour, 6 hours, and 24 hours after reperfusion. The liver tissue sections were applied to IMS (m/z 200-2000). Candidate molecules were identified by tandem mass spectrometry. Imaging mass spectrometry (IMS) revealed a significant increase in the taurine conjugates of dihydroxycholanoic acid (TDHCA) during ischemia and a tendency to return to the basal level after reperfusion. Notably, high-resolution measurements revealed focal accumulation of TDHCA in the intrahepatic bile duct with ischemic time. In conclusion, IMS is a useful method to detect minute changes provoked by ischemia, which are barely detectable in assays involving homogenization. Accordingly, focal accumulation of TDHCA during ischemia may be a candidate marker for predicting later IRI.


Assuntos
Ácido Desoxicólico/análise , Fígado , Traumatismo por Reperfusão , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Isquemia Quente/efeitos adversos , Animais , Modelos Animais de Doenças , Fígado/química , Masculino , Ratos , Taurina/análise
10.
Neurosci Lett ; 708: 134176, 2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31173847

RESUMO

Circulating microRNAs (miRNAs) in peripheral blood have been extensively investigated as biomarkers for early diagnosis and monitoring of disease progression. However, their cellular origin as well as their link to the pathophysiology, especially neurodegenerative disease, remains largely unknown. In the present study, we isolated neuron-derived extracellular vesicles (EVs) in plasma by immunoaffinity purification and comprehensively analyzed their miRNA expression profiles using microarray. A total of 30 miRNAs were differentially regulated in amyotrophic lateral sclerosis (ALS) plasma relative to healthy control plasma. Gene ontology analysis revealed that biological processes implicated in both up-regulated and down-regulated miRNAs were involved in synaptic vesicle-related pathways. Especially, 4 miRNAs in plasma neuro-derived EVs seemed to be regulated in the similar manner as those in formalin-fixed paraffin-embedded motor cortex samples from ALS patients. The target genes for the 4 miRNAs partly overlapped in STX1B, RAB3B, and UNC13A genes. UNC13A has been reported to be associated with increased odds of sporadic ALS in multiple genome-wide association studies. Our data suggest that miRNAs extracted from neuron-derived EVs in plasma reflect miRNA alterations in the brain as potential biomarkers of ALS.


Assuntos
Esclerose Lateral Amiotrófica/genética , Vesículas Extracelulares/metabolismo , MicroRNAs/sangue , Neurônios/metabolismo , Esclerose Lateral Amiotrófica/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Gravidez
11.
Mol Brain ; 12(1): 49, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088501

RESUMO

MicroRNAs (miRNAs) are endogenous small (18-25 nt), single-stranded, non-coding RNAs that play key roles in post-transcriptional gene expression regulation. The expression profiles of miRNAs in biofluids and tissues change in various diseases. Multiple system atrophy (MSA) and Parkinson's disease (PD) are both categorized as α-synucleinopathies and often present with similar clinical manifestations. This study aimed to identify miRNAs that are differently expressed in plasma samples of PD patients, MSA patients, and healthy controls. We used microarray analysis to screen for miRNAs that are up- and down-regulated in these patients and analyzed the relative-quantitative expression levels of the identified miRNAs by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p showed significantly different expression levels among patients with MSA-C, MSA-P, or PD, and healthy controls. Hsa-miR-671-5p levels were lower in the MSA-P and PD than the MSA-C and control groups, hsa-miR-19b-3p levels were higher in the PD than the other groups, and hsa-miR-24-3p levels were higher in the PD than the MSA-C group. Hsa-miR-671-5p was the first miRNA shown to be expressed differently between MSA-C and MSA-P in plasma. Interestingly, the expression levels of hsa-miR-19b-3p and hsa-miR-24-3p were positively correlated, indicating that these miRNAs may be involved in the same processes in PD pathogenesis. Our findings suggest that hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p may reflect the pathophysiology or symptoms of PD and MSA.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/sangue , MicroRNAs/genética , Atrofia de Múltiplos Sistemas/sangue , Atrofia de Múltiplos Sistemas/genética , Doença de Parkinson/sangue , Doença de Parkinson/genética , Estudos de Casos e Controles , Regulação para Baixo/genética , Feminino , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima/genética
12.
Clin Park Relat Disord ; 1: 82-85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-34316606

RESUMO

BACKGROUND: Patients with Parkinson's disease and related disorders (PDRD) may exhibit dropped head syndrome (DHS), which does not yet have an effective treatment. OBJECTIVES: To evaluate the effect of combining lidocaine injection into the bilateral scalene muscles and neck corset wearing on dropped head syndrome. METHODS: We performed needle electromyography assessments of the scalene, sternocleidomastoid (SCM), levator scapulae, splenius capitis, and trapezius muscles. Patients received 2.5-5 ml injections of 1% lidocaine into both sides of the scalene muscles for 4/5 consecutive days and were instructed to wear a neck corset. We measured the neck flexion angle, which formed between the horizontal line and the straight line passing through the ear canal and orbital fossa, before (baseline) and after (Day 8 and Day 90) the intervention. RESULTS: Seven males and eight females (mean age, 68.9 years; range 56 to 85 years) who had PDRD with dropped head syndrome were enrolled in this study. Needle electromyography examination revealed abnormal discharge of the scalene muscles in all patients when the neck position was corrected; however, some patients did not show abnormal discharge of the SCM muscle. At Day 8, we observed an improvement of the neck flexion angle in 13 of the 15 patients, from an average of 27.7°â€¯±â€¯13.9° to 11.7 ±â€¯14.6°. At Day 90, the average neck flexion angle was 15.3°â€¯±â€¯17.2°. CONCLUSIONS: Combining lidocaine injection into the scalene muscles and neck corset wearing is an effective treatment regimen for DHS in patients with PDRD.

13.
BMC Med Genomics ; 11(1): 72, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30157848

RESUMO

BACKGROUND: Moyamoya disease (MMD) is characterized by progressive stenosis of intracranial arteries in the circle of Willis with unknown etiology even after the identification of a Moyamoya susceptible gene, RNF213. Recently, differences in epigenetic regulations have been investigated by a case-control study in MMD. Here, we employed a disease discordant monozygotic twin-based study design to unmask potential confounders. METHODS: Circulating genome-wide microRNA (miRNome) profiling was performed in MMD-discordant monozygotic twins, non-twin-MMD patients, and non-MMD healthy volunteers by microarray followed by qPCRvalidation, using blood samples. Differential plasma-microRNAs were further quantified in endothelial cells differentiated from iPS cell lines (iPSECs) derived from another independent non-twin cohort. Lastly, their target gene expression in the iPSECs was analyzed. RESULTS: Microarray detected 309 plasma-microRNAs in MMD-discordant monozygotic twins that were also detected in the non-twin cohort. Principal component analysis of the plasma-microRNA expression level demonstrated distinct 2 groups separated by MMD and healthy control in the twin- and non-twin cohorts. Of these, differential upregulations of hsa-miR-6722-3p/- 328-3p were validated in the plasma of MMD (absolute log2 expression fold change (logFC) > 0.26 for the twin cohort; absolute logFC > 0.26, p < 0.05, and q < 0.15 for the non-twin cohort). In MMD derived iPSECs, hsa-miR-6722-3p/- 328-3p showed a trend of up-regulation with a 3.0- or higher expression fold change. Bioinformatics analysis revealed that 41 target genes of miR-6722-3p/- 328-3p were significantly down-regulated in MMD derived iPSECs and were involved in STAT3, IGF-1-, and PTEN-signaling, suggesting a potential microRNA-gene expression interaction between circulating plasma and endothelial cells. CONCLUSIONS: Our MMD-discordant monozygotic twin-based study confirmed a novel circulating microRNA signature in MMD as a potential diagnostic biomarker minimally confounded by genetic heterogeneity. The novel circulating microRNA signature can contribute for the future functional microRNA analysis to find new diagnostic and therapeutic target of MMD.


Assuntos
Células Endoteliais/metabolismo , Perfilação da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/metabolismo , MicroRNAs/genética , Doença de Moyamoya/sangue , Doença de Moyamoya/genética , Gêmeos Monozigóticos , Adolescente , Estudos de Casos e Controles , Linhagem Celular , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Doença de Moyamoya/patologia
14.
Sci Rep ; 8(1): 819, 2018 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-29339765

RESUMO

Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer's disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis. Whole-exome analysis of this family identified a novel missense mutation in BSN. Within the pedigree, the detected BSN mutation was found only in affected individuals. Further genetic analyses were conducted in probands from four other pedigrees with PSP-like syndrome and in 41 sporadic cases. Three missense mutations in BSN that are very rarely listed in databases of healthy subjects were found in four sporadic cases. Western blot analysis of tau following the overexpression of wild-type or mutated BSN revealed the possibility that wild-type BSN reduced tau accumulation, while mutated BSN lost this function. An association between BSN and neurological diseases has not been previously reported. Our results revealed that the neurodegenerative disorder associated with the original proband's pedigree is a novel tauopathy, differing from known dementia and parkinsonism syndromes, including PSP.


Assuntos
Saúde da Família , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/genética , Paralisia Supranuclear Progressiva/genética , Paralisia Supranuclear Progressiva/patologia , Hipocampo/patologia , Humanos
15.
Mol Brain ; 10(1): 54, 2017 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-29187220

RESUMO

Genomic variation includes single-nucleotide variants, small insertions or deletions (indels), and copy number variants (CNVs). CNVs affect gene expression by altering the genome structure and transposable elements within a region. CNVs are greater than 1 kb in size; hence, CNVs can produce more variation than can individual single-nucleotide variations that are detected by next-generation sequencing. Multiple system atrophy (MSA) is an α-synucleinopathy adult-onset disorder. Pathologically, it is characterized by insoluble aggregation of filamentous α-synuclein in brain oligodendrocytes. Generally, MSA is sporadic, although there are rare cases of familial MSA. In addition, the frequencies of the clinical phenotypes differ considerably among countries. Reports indicate that genetic factors play roles in the mechanisms involved in the pathology and onset of MSA. To evaluate the genetic background of this disorder, we attempted to determine whether there are differences in CNVs between patients with MSA and normal control subjects. We found that the number of CNVs on chromosomes 5, 22, and 4 was increased in MSA; 3 CNVs in non-coding regions were considered risk factors for MSA. Our results show that CNVs in non-coding regions influence the expression of genes through transcription-related mechanisms and potentially increase subsequent structural alterations of chromosomes. Therefore, these CNVs likely play roles in the molecular mechanisms underlying MSA.


Assuntos
Variações do Número de Cópias de DNA/genética , Genômica , Adulto , Idoso , Atrofia , Análise por Conglomerados , Feminino , Ontologia Genética , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
16.
Rinsho Shinkeigaku ; 57(10): 567-572, 2017 10 27.
Artigo em Japonês | MEDLINE | ID: mdl-28966227

RESUMO

A 24-year-old woman visited our hospital with a complaint of walking disability. She had no family history of consanguineous marriage, and her developmental history was unremarkable, with good physical performance just before the onset. At the age of 13, she developed difficulty in walking and visited a pediatrician. Her serum CK level was 10,000 IU/l and she was diagnosed with muscular dystrophy by muscle biopsy. At the age of 16, she became wheelchair dependent and was admitted to our hospital. Physical examination revealed diffuse muscle atrophy and proximal weakness, with no calf hypertrophy or selectivity of muscle involvement. Needle EMG and MR images indicated inflammatory myopathy. Muscle biopsy revealed necrotic and regenerating fibers and lymphocyte infiltration. She was re-diagnosed with inflammatory myopathy and recovered walking capacity after immunotherapy. Subsequently, she was tested positive for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. To distinguish treatable inflammatory myopathy from muscular dystrophy, a comprehensive assessment of patient history, family history, selectivity of muscle involvement, findings suggestive of inflammation in EMG and CT/MR imaging, and muscle pathology is necessary.


Assuntos
Autoanticorpos/sangue , Hidroximetilglutaril-CoA Redutases/imunologia , Doenças Musculares/diagnóstico , Adulto , Idade de Início , Biomarcadores/sangue , Doença Crônica , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoterapia , Doenças Musculares/imunologia , Doenças Musculares/terapia , Distrofias Musculares , Necrose , Resultado do Tratamento , Adulto Jovem
17.
J Hum Genet ; 62(9): 857-859, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28490766

RESUMO

Spinocerebellar ataxia (SCA) is a group of dominantly inherited heterogeneous disorders in which 43 subtypes have been identified to date. Recently, Japanese and French families with SCA type 42 (SCA42) were found to have a missense mutation (c.5144G>A; R1715H) in CACNA1G. We performed genetic analysis of 84 unrelated families to find the prevalence of SCA42 in Japan. Two families were found to have the previously reported missense mutation. Clinical presentations of the affected members of these families were similar to those of the previously reported French and Japanese families. Our study demonstrates that SCA42 exists in small numbers in Japan, and further supports the idea that SCA42 is a slowly progressive, pure cerebellar ataxia.


Assuntos
Mutação , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Encéfalo/patologia , Canais de Cálcio Tipo T/genética , Análise Mutacional de DNA , Éxons , Feminino , Testes Genéticos , Humanos , Japão/epidemiologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Linhagem , Fenótipo , Locos de Características Quantitativas , Ataxias Espinocerebelares/epidemiologia
18.
J Infect Chemother ; 22(1): 58-60, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26419364

RESUMO

Lemierre's syndrome is an oropharyngeal bacterial infection characterized by rapidly progressive septic thrombophlebitis of the internal jugular vein. A lack of appropriate antibiotic therapy can be life-threatening. We describe the case of a 39-year-old man with Lemierre's syndrome who presented with long-lasting orbital pain and acute exophthalmos 6 weeks after initial infection. This report is to help clinicians consider the diagnosis of Lemierre's syndrome when encountering a patient with long-lasting orbital pain and acute exophthalmos. Neck ultrasonography is useful for detecting thrombophlebitis of the internal jugular vein in Lemierre's syndrome patients.


Assuntos
Exoftalmia , Síndrome de Lemierre , Dor , Adulto , Humanos , Veias Jugulares/patologia , Síndrome de Lemierre/diagnóstico por imagem , Síndrome de Lemierre/fisiopatologia , Masculino , Órbita/fisiopatologia , Tromboflebite/diagnóstico , Tromboflebite/etiologia , Ultrassonografia
19.
Mol Brain ; 8(1): 67, 2015 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-26497046

RESUMO

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, which leads to the loss of upper and lower motor neurons, with a currently unknown etiology. Specific biomarkers could help in early detection and diagnosis, and could also act as indicators of disease progression and therapy effectiveness. MicroRNAs (miRNAs) are small (18-25 nucleotides), single-stranded non-coding RNA molecules that play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression, and are essential for nervous system development. Many of the genes associated with genetic ALS have pathological biological pathways related to RNA metabolism, and their pathogenesis may be affecting the maturing processes of miRNA. RESULTS: We compared miRNA from the plasma of sALS patients and healthy controls using two cohorts; a discovery cohort analyzed with microarray (16 sALS patients and ten healthy controls) and a validation cohort confirmed with qPCR (48 sALS patients, 47 healthy controls and 30 disease controls). We measured the total amount of extracted RNA along with a spike-in control that ensured the quality of our quantification. A percentage of the 10-40 nt RNAs extracted from the total RNA showed a significant increase in ALS patients. There was a negative correlation between total RNA concentration and disease duration from onset to end point. Three of the miRNAs were up-regulated and six were down-regulated significantly in the discovery cohort. Since an internal control is required as a sample stability indicator of both the patients and controls in microarray analysis, we selected the miRNA showing the smallest dispersion and equivalency between the two groups' mean value, and decided to use hsa-miR-4516. We found hsa-miR-4649-5p to be up-regulated, and hsa-miR-4299 to be down-regulated, where each was not influenced by clinical characteristics. EPHA4, a target gene linked to the nervous system which has also been reported to be a disease modifier of ALS, is the common and most notable target gene of hsa-miR-4649-5p and hsa-miR-4299. CONCLUSION: We have shown the relationship circulating plasma miRNA has with both healthy controls and diseased patients. Hsa-miR-4649-5p and hsa-miR-4299 have the potential to be ALS diagnosis biomarkers.


Assuntos
Esclerose Lateral Amiotrófica/sangue , Biomarcadores/sangue , MicroRNAs/sangue , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Regulação para Baixo/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Doença de Parkinson/genética , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de Tempo , Regulação para Cima/genética
20.
Cerebrovasc Dis Extra ; 5(2): 84-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26265911

RESUMO

BACKGROUND: Atrial fibrillation (AF) is an important risk factor for transient ischemic attack (TIA). However, little is known about the characteristics of TIA patients with AF. This study investigated the characteristics of such patients, using data from a retrospective, observational, multicenter study. METHODS: TIA patients admitted to 13 stroke centers in Japan within 7 days of onset between January 2008 and December 2009 were included. The present analyses compared baseline characteristics, clinical symptoms, findings from diffusion-weighted imaging (DWI), and clinical outcomes between patients with and without AF (AF and non-AF groups). RESULTS: A total of 464 patients (292 men; mean age 68.5 ± 13.2 years) were registered. Of these, 79 patients (17%) had AF. Patients in the AF group were older (73.9 ± 9.1 vs. 67.4 ± 13.6 years, p < 0.001) and more likely to show disturbance of consciousness (13 vs. 6%, p = 0.046) and aphasia (9 vs. 3%, p = 0.007) than patients in the non-AF group. Although no difference in the overall DWI-positive rate was seen between the groups (28 vs. 20%, p = 0.102), a single lesion (23 vs. 10%, p < 0.001), a lesion ≥15 mm (11 vs. 4%, p = 0.006), and a single lesion ≥15 mm (11 vs. 2%, p < 0.001) on DWI were more frequent in the AF group. Multivariate logistic regression analysis identified increased age [odds ratio (OR) 1.04; 95% confidence interval (CI) 1.02-1.07] and DWI single lesion ≥15 mm (OR 5.67; 95% CI 1.92-16.7) as independently associated with the presence of AF. CONCLUSIONS: In this study, 17% of our TIA patients had AF. We found an association between the acute ischemic lesion pattern on DWI of a single lesion ≥15 mm and AF in TIA patients. These results might lead to a better diagnosis of TIA patients with AF.


Assuntos
Fibrilação Atrial/patologia , Ataque Isquêmico Transitório/patologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Ataque Isquêmico Transitório/epidemiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
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