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1.
Cell Mol Life Sci ; 77(18): 3597-3609, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31758234

RESUMO

The bHLH transcription factor Olig2 is required for sequential cell fate determination of both motor neurons and oligodendrocytes and for progenitor proliferation in the central nervous system. However, the role of Olig2 in peripheral sensory neurogenesis remains unknown. We report that Olig2 is transiently expressed in the newly differentiated olfactory sensory neurons (OSNs) and is down-regulated in the mature OSNs in mice from early gestation to adulthood. Genetic fate mapping demonstrates that Olig2-expressing cells solely give rise to OSNs in the peripheral olfactory system. Olig2 depletion does not affect the proliferation of peripheral olfactory progenitors and the fate determination of OSNs, sustentacular cells, and the olfactory ensheathing cells. However, the terminal differentiation and maturation of OSNs are compromised in either Olig2 single or Olig1/Olig2 double knockout mice, associated with significantly diminished expression of multiple OSN maturation and odorant signaling genes, including Omp, Gnal, Adcy3, and Olfr15. We further demonstrate that Olig2 binds to the E-box in the Omp promoter region to regulate its expression. Taken together, our results reveal a distinctly novel function of Olig2 in the periphery nervous system to regulate the terminal differentiation and maturation of olfactory sensory neurons.


Assuntos
Diferenciação Celular , Neurônios Receptores Olfatórios/metabolismo , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem da Célula , Proliferação de Células , Proteína Duplacortina , Embrião de Mamíferos/metabolismo , Embrião de Mamíferos/patologia , Camundongos , Camundongos Transgênicos , Proteína de Marcador Olfatório/genética , Mucosa Olfatória/citologia , Mucosa Olfatória/metabolismo , Fator de Transcrição 2 de Oligodendrócitos/deficiência , Fator de Transcrição 2 de Oligodendrócitos/genética , Regiões Promotoras Genéticas , Fatores de Transcrição SOXB1/deficiência , Fatores de Transcrição SOXB1/genética , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
2.
Biochem Biophys Res Commun ; 496(4): 1302-1307, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29410176

RESUMO

After traumatic spinal cord injury (SCI), a scar may form with a fibrotic core (fibrotic scar) and surrounding reactive astrocytes (glial scar) at the lesion site. The scar tissue is considered a major obstacle preventing regeneration both as a physical barrier and as a source for secretion of inhibitors of axonal regeneration. Understanding the mechanism of scar formation and how to control it may lead to effective SCI therapies. Using a compression-SCI model on adult transgenic mice, we demonstrate that the canonical Wnt/ß-catenin signaling reporter TOPgal (TCF/Lef1-lacZ) positive cells appeared at the lesion site by 5 days, peaked on 7 days, and diminished by 14 days post injury. Using various representative cell lineage markers, we demonstrate that, these transiently TOPgal positive cells are a group of Fibronectin(+);GFAP(-) fibroblast-like cells in the core scar region. Some of them are proliferative. These results indicate that Wnt/ß-catenin signaling may play a key role in fibrotic scar formation after traumatic spinal cord injury.


Assuntos
Cicatriz/metabolismo , Cicatriz/patologia , Compressão da Medula Espinal/metabolismo , Compressão da Medula Espinal/patologia , Medula Espinal/patologia , Via de Sinalização Wnt , beta Catenina/metabolismo , Animais , Cicatriz/etiologia , Fibrose , Proteína Glial Fibrilar Ácida , Camundongos , Camundongos Transgênicos , Medula Espinal/metabolismo , Compressão da Medula Espinal/complicações
4.
Stem Cells ; 32(1): 45-58, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24115331

RESUMO

The Wnt/ß-catenin pathway is a critical stem cell regulator and plays important roles in neuroepithelial cells during early gestation. However, the role of Wnt/ß-catenin signaling in radial glia, a major neural stem cell population expanded by midgestation, remains poorly understood. This study shows that genetic ablation of ß-catenin with hGFAP-Cre mice inhibits neocortical formation by disrupting radial glial development. Reduced radial glia and intermediate progenitors are found in the ß-catenin-deficient neocortex during late gestation. Increased apoptosis and divergent localization of radial glia in the subventricular zone are also observed in the mutant neocortex. In vivo and in vitro proliferation and neurogenesis as well as oligodendrogenesis by cortical radial glia or by dissociated neural stem cells are significantly defective in the mutants. Neocortical layer patterning is not apparently altered, while astrogliogenesis is ectopically increased in the mutants. At the molecular level, the expression of the transcription factor Pax6 is dramatically diminished in the cortical radial glia and the sphere-forming neural stem cells of ß-catenin-deficient mutants. Chromatin immunoprecipitation and luciferase assays demonstrate that ß-catenin/Tcf complex binds to Pax6 promoter and induces its transcriptional activities. The forced expression of Pax6 through lentiviral transduction partially rescues the defective proliferation and neurogenesis by ß-catenin-deficient neural stem cells. Thus, Pax6 is a novel downstream target of the Wnt/ß-catenin pathway, and ß-catenin/Pax6 signaling plays critical roles in self-renewal and neurogenesis of radial glia/neural stem cells during neocortical development.


Assuntos
Proteínas do Olho/metabolismo , Proteínas de Homeodomínio/metabolismo , Neocórtex/citologia , Células-Tronco Neurais/citologia , Neurogênese/fisiologia , Fatores de Transcrição Box Pareados/metabolismo , Proteínas Repressoras/metabolismo , beta Catenina/metabolismo , Animais , Diferenciação Celular/fisiologia , Processos de Crescimento Celular/fisiologia , Camundongos , Camundongos Transgênicos , Neocórtex/metabolismo , Células-Tronco Neurais/metabolismo , Neuroglia/citologia , Neuroglia/metabolismo , Fator de Transcrição PAX6 , Transdução de Sinais , Transfecção , Via de Sinalização Wnt , beta Catenina/genética
5.
FASEB J ; 27(6): 2111-21, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23413357

RESUMO

To identify human bone marrow stromal cell (BMSC) subsets with enhanced ability to engraft/contribute to the resident intestinal cellular pool, we transplanted clonally derived BMSCs into fetal sheep. Analysis at 75 d post-transplantation showed 2 of the 6 clones engrafting the intestine at 4- to 5-fold higher levels (5.03±0.089 and 5.04±0.15%, respectively) than the other clones (P<0.01), correlating with the percentage of donor-derived Musashi-1(+) (12.01-14.17 vs. 1.2-3.8%; P<0.01) or leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5)(+) cells within the intestinal stem cell (ISC) region. Phenotypic and transcriptome analysis determined that the clones with enhanced intestinal contribution expressed high levels of Ephrin type B receptor 2 (EphB2). Intestinal explants demonstrated proliferation of the engrafted cells and ability to generate crypt-like structures in vitro still expressing EphB2. Additional transplants based on BMSC EphB2 expression demonstrated that, at 7 d post-transplant, the EphB2(high) BMSCs engrafted in the ISC region at levels of 2.1 ± 0.2%, while control EphB2(low) BMSCs engrafted at 0.3 ± 0.1% (P<0.01). Therefore we identified a marker for isolating and culturing an expandable subpopulation of BMSCs with enhanced intestinal homing and contribution to the ISC region.


Assuntos
Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Células-Tronco Mesenquimais/classificação , Células-Tronco Mesenquimais/metabolismo , Receptor EphB2/metabolismo , Animais , Biomarcadores/metabolismo , Linhagem da Célula , Feminino , Feto , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Mucosa Intestinal/embriologia , Intestino Delgado/citologia , Intestino Delgado/embriologia , Intestino Delgado/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Gravidez , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Receptor EphB2/genética , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Ovinos , Nicho de Células-Tronco , Transcriptoma , Transplante Heterólogo
6.
J Cell Sci ; 124(Pt 9): 1553-63, 2011 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-21486944

RESUMO

The mammalian olfactory epithelium (OE) has a unique stem cell or progenitor niche, which is responsible for the constant peripheral neurogenesis throughout the lifespan of the animal. However, neither the signals that regulate the behavior of these cells nor the lineage properties of the OE stem cells are well understood. Multiple Wnt signaling components exhibit dynamic expression patterns in the developing OE. We generated Wnt signaling reporter TOPeGFP transgenic mice and found TOPeGFP activation predominantly in proliferating Sox2(+) OE basal cells during early postnatal development. FACS-isolated TOPeGFP(+) OE basal cells are required, but are not sufficient, for formation of spheres. Wnt3a significantly promotes the proliferation of the Sox2(+) OE sphere cells. Wnt-stimulated OE sphere cells maintain their multipotency and can differentiate into most types of neuronal and non-neuronal epithelial cells. Also, Wnt activators shift the production of differentiated cells toward olfactory sensory neurons. Moreover, TOPeGFP(+) cells are robustly increased in the adult OE after injury. In vivo administration of Wnt modulators significantly alters the regeneration potential. This study demonstrates the role of the canonical Wnt signaling pathway in the regulation of OE stem cells or progenitors during development and regeneration.


Assuntos
Diferenciação Celular/fisiologia , Neurogênese/fisiologia , Mucosa Olfatória/citologia , Células-Tronco/citologia , Animais , Apoptose/genética , Apoptose/fisiologia , Diferenciação Celular/genética , Proliferação de Células , Células Cultivadas , Citometria de Fluxo , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Transgênicos , Neurogênese/genética , Neurônios/citologia , Neurônios/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Proteína Wnt3 , Proteína Wnt3A
7.
J Arrhythm ; 39(4): 499-506, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37560279

RESUMO

Background: Detecting unknown atrial fibrillation (AF) would provide an opportunity to prevent ischemic stroke by instituting appropriate anticoagulation. Although opportunistic screening of older patients is recommended in current guidelines, which patients may benefit from intensive AF screening remains unclear. We sought to clarify the risk factor profile for newly diagnosed AF in annual health examinations of a Japanese adult cohort. Methods: Among 141 441 Japanese patients who underwent annual health examinations in 2014, 87 872 patients aged ≥20 years without known AF who had undergone electrocardiography were analyzed (mean age: 47 ± 12 years; 64% men). The absence of known AF was confirmed by prior electrocardiography in 2012 and/or 2013. Newly diagnosed AF was observed in 244 patients in 2014-2017 (mean age: 62 ± 12 years; 83% men). Results: In the multivariable analysis, waist circumference obesity (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.13-1.99; p = .005) high blood pressure (HR, 1.9; 95% CI, 1.01-3.59; p = .047), on-treatment hypertension (HR, 1.53; 95% CI, 1.01-2.31; p = .046), and daily alcohol drinking (HR, 2.18; 95% CI, 1.52-3.12; p < .001) were significantly associated with newly diagnosed AF. Conclusions: In this Japanese cohort, waist circumference obesity, hypertension, and alcohol drinking were independent predictors of newly diagnosed AF in annual medical examinations. This finding encourages further evaluation of systematic AF screening programs in at-risk populations.

8.
Dev Biol ; 350(2): 511-9, 2011 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21185284

RESUMO

The canonical Wnt/ß-catenin signaling plays essential role in development and diseases. Previous studies have implicated the canonical Wnt/ß-catenin signaling in the regulation of normal palate development, but functional Wnt/ß-catenin signaling and its tissue-specific activities remain to be accurately elucidated. In this study, we show that functional Wnt/ß-catenin signaling operates primarily in the palate epithelium, particularly in the medial edge epithelium (MEE) of the developing mouse palatal shelves, consistent with the expression patterns of ß-catenin and several Wnt ligands and receptors. Epithelial specific inactivation of ß-catenin by the K14-Cre transgenic allele abolishes the canonical Wnt signaling activity in the palatal epithelium and leads to an abnormal persistence of the medial edge seam (MES), ultimately causing a cleft palate formation, a phenotype resembling that in Tgfß3 mutant mice. Consistent with this phenotype is the down-regulation of Tgfß3 and suppression of apoptosis in the MEE of the ß-catenin mutant palatal shelves. Application of exogenous Tgfß3 to the mutant palatal shelves in organ culture rescues the midline seam phenotype. On the other hand, expression of stabilized ß-catenin in the palatal epithelium also disrupts normal palatogenesis by activating ectopic Tgfß3 expression in the palatal epithelium and causing an aberrant fusion between the palate shelf and mandible in addition to severely deformed palatal shelves. Collectively, our results demonstrate an essential role for Wnt/ß-catenin signaling in the epithelial component at the step of palate fusion during palate development by controlling the expression of Tgfß3 in the MEE.


Assuntos
Palato/embriologia , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta3/genética , Proteínas Wnt/fisiologia , beta Catenina/fisiologia , Animais , Fissura Palatina/etiologia , Perfilação da Expressão Gênica , Camundongos
9.
Development ; 136(18): 3161-71, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19700620

RESUMO

Neither the mechanisms that govern lip morphogenesis nor the cause of cleft lip are well understood. We report that genetic inactivation of Lrp6, a co-receptor of the Wnt/beta-catenin signaling pathway, leads to cleft lip with cleft palate. The activity of a Wnt signaling reporter is blocked in the orofacial primordia by Lrp6 deletion in mice. The morphological dynamic that is required for normal lip formation and fusion is disrupted in these mutants. The expression of the homeobox genes Msx1 and Msx2 is dramatically reduced in the mutants, which prevents the outgrowth of orofacial primordia, especially in the fusion site. We further demonstrate that Msx1 and Msx2 (but not their potential regulator Bmp4) are the downstream targets of the Wnt/beta-catenin signaling pathway during lip formation and fusion. By contrast, a ;fusion-resistant' gene, Raldh3 (also known as Aldh1a3), that encodes a retinoic acid-synthesizing enzyme is ectopically expressed in the upper lip primordia of Lrp6-deficient embryos, indicating a region-specific role of the Wnt/beta-catenin signaling pathway in repressing retinoic acid signaling. Thus, the Lrp6-mediated Wnt signaling pathway is required for lip development by orchestrating two distinctively different morphogenetic movements.


Assuntos
Proteínas Relacionadas a Receptor de LDL/metabolismo , Lábio/embriologia , Morfogênese/fisiologia , Transdução de Sinais/fisiologia , Proteínas Wnt/metabolismo , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Animais , Apoptose/fisiologia , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Proliferação de Células , Fenda Labial/metabolismo , Fenda Labial/patologia , Embrião de Mamíferos/anatomia & histologia , Embrião de Mamíferos/fisiologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas Relacionadas a Receptor de LDL/genética , Lábio/anatomia & histologia , Lábio/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Fator de Transcrição MSX1/genética , Fator de Transcrição MSX1/metabolismo , Camundongos , Camundongos Transgênicos , Regiões Promotoras Genéticas , Retinal Desidrogenase , Proteínas Wnt/genética
10.
J Bone Miner Metab ; 29(2): 208-16, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20711620

RESUMO

Bone development up to early adulthood plays an important role in determining the risk of osteoporosis later in life. However, bone development in children has not been fully documented by longitudinal studies in Japanese children. The purpose of this study is to determine the degree of tracking of areal bone mineral density (aBMD) from pre-puberty to 6-year follow-up, and to determine the target period to achieve maximal peak aBMD. This study was conducted as the pediatric part of a larger cohort study, the Japanese Population-based Osteoporosis (JPOS) study. Of 448 children aged 9-12 years who completed the baseline survey, 225 participated in the follow-up study 6 years later (follow-up rate: 50.2%). aBMD at the forearm was measured using dual-energy X-ray absorptiometry. aBMD values in pre-pubertal children at baseline showed a significant tracking correlation with aBMD obtained at 6-year follow-up in both genders (boys r = 0.655, girls r = 0.759). Although boys and girls in the lowest quartile of aBMD pre-pubertally had greater annual increases in aBMD from pre-puberty to 6-year follow-up than those in other aBMD quartiles, they still showed the lowest mean aBMD at 6-year follow-up. Children with lower pre-pubertal aBMD showed greater increases in BMD up until 6-year follow-up, but the increase was not great enough to catch up with other children. About 50% of the variance in aBMD at 6-year follow-up was determined by the aBMD achieved during the pre-pubertal period. Activities that increase aBMD are important not only for children during puberty, but also for younger pre-pubertal children.


Assuntos
Densidade Óssea , Osteoporose/metabolismo , Puberdade/metabolismo , Absorciometria de Fóton , Povo Asiático , Estatura , Peso Corporal , Criança , Estudos de Coortes , Feminino , Humanos , Masculino
11.
Dev Dyn ; 239(1): 318-26, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19653321

RESUMO

Lrp6 is a key coreceptor in the canonical Wnt pathway that is widely involved in tissue/organ morphogenesis. We generated a loxP-floxed Lrp6 mouse line. Crossing with a general Cre deleter, we obtained the Lrp6-floxdel mice, in which the loxP-floxed exon 2 of Lrp6 gene has been deleted ubiquitously. The homozygotes of Lrp6-floxdel mice reproduced typical defects as seen in the conventional Lrp6-deficient mice, such as defects in eye, limb, and neural tube, and die around birth. We also found new phenotypes including cleft palate and agenesis of external genitalia in the Lrp6-floxdel mice. In addition, the Lrp6-deficient embryos are known to be defective in other systems and internal organs including the heart and brain. Thus, by selectively crossing with a lineage-specific or inducible Cre mouse line, the Lrp6 conditional gene-targeting mice will allow us to model specific types of birth defects for mechanism and prevention studies.


Assuntos
Anormalidades Congênitas/genética , Modelos Animais de Doenças , Proteínas Relacionadas a Receptor de LDL/deficiência , Animais , Northern Blotting , Cruzamentos Genéticos , Primers do DNA/genética , Eletroporação , Éxons/genética , Marcação de Genes , Immunoblotting , Proteínas Relacionadas a Receptor de LDL/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Camundongos , Microinjeções , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
J Diabetes Investig ; 12(9): 1680-1688, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33567117

RESUMO

AIMS/INTRODUCTION: Fragmented QRS (fQRS) on electrocardiography is a marker of myocardial fibrosis and myocardial scar formation. This study aimed to clarify the relationship of fQRS with diabetes mellitus and metabolic syndrome (MetS) in Japanese patients. MATERIALS AND METHODS: Approximately 702 individuals who had a routine health checkup at the Hokuriku Health Service Association (Toyama, Japan) in October 2014 were enrolled and categorized into one of the following four groups based on MetS and diabetes mellitus status: with diabetes mellitus (+) MetS+ (164 participants); diabetes mellitus+ without MetS (Mets-; 103 participants); diabetes mellitus- MetS+ (133 participants); and diabetes mellitus- MetS- (302 participants). fQRS was assessed using the results of electrocardiography. RESULTS: The prevalence of fQRS was statistically higher in patients with diabetes mellitus+ MetS+ (37%) and diabetes mellitus+ MetS- (35%), than those with diabetes mellitus- MetS+ (14%) or diabetes mellitus- MetS- (10%; P < 0.0001). Significant differences were observed between the fQRS(+) and fQRS(-) groups for age, sex, waist circumference, heart rate, hypertension, hemoglobin A1c, total cholesterol, MetS and diabetes mellitus. The area under the receiver operating characteristic curve for traditional risk factors and diabetes mellitus was 0.72 (P = 0.0007, 95% confidence interval 0.67-0.76), and for traditional risk factors and MetS it was 0.67 (P = 0.28, 95% confidence interval 0.62-0.72). Patients with diabetes mellitus had more than threefold higher likelihood of showing fQRS (odds ratio 3.41; 95% confidence interval 2.25-5.22; P < 0.0001) compared with the reference group without diabetes mellitus, after adjusting for age, sex, dyslipidemia, hypertension and waist circumference. CONCLUSIONS: fQRS was observed more frequently in diabetes mellitus patients than in MetS and control individuals. Diabetes mellitus was the most significant determinant for fQRS among MetS and other traditional metabolic risk factors.


Assuntos
Diabetes Mellitus/fisiopatologia , Cardiomiopatias Diabéticas/epidemiologia , Eletrocardiografia/métodos , Síndrome Metabólica/fisiopatologia , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/patologia , Humanos , Prognóstico
13.
BMJ Open ; 10(7): e035650, 2020 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-32690510

RESUMO

OBJECTIVES: International guidelines recommend opportunistic screening for atrial fibrillation (AF); however, there is no current data to inform how often to repeat screening. We aimed to investigate the incremental annual yield and stroke risk of new AF cases in individuals screened annually over 4 years. DESIGN: A retrospective cohort study. SETTING: Hokuriku Health Service Association, Toyama prefecture, Japan. PARTICIPANTS: Employees and their families receiving annual health examinations from Hokuriku Health Service Association. INTERVENTION: Each subject received an annual health examination (including 12-lead ECG) from 2014 to 2017. Only subjects with baseline ECGs in 2012 and/or 2013 were included. MAIN OUTCOME MEASURES: Rates (cases/100 person-years) of new AF identified each year for 4 consecutive years of screening (stratified according to gender and age groups). Calculated stroke risk of new AF cases using modified CHA2DS2-VASc scores (without heart failure data) (CHA2DS2VASc = C: congestive heart failure [1 point]; H: hypertension [1 point]; A2: age 65-74 years [1 point] or age ≥75 years [2 points]; D: diabetes mellitus [1 point]; S: prior stroke or transient ischemic attack [2 points]; VA: vascular disease [1 point]; and Sc: sex category [female] [1 point]) RESULTS: In 2014, 88 218 subjects had an ECG (46.8±12.5 years; 64% men): identifying 346 (0.39%) known AF and 69 (0.08%) new AF. The incidence rate of new AF increased with age from 0.01% (<50 years) to 0.98% (≥75 years) and was higher in men (0.1%) than women (0.05%). Repeated annual screening over 4 years identified a consistent new AF yield 0.06%-0.10% per year (0.33%-0.55% ≥65 years). Forty-two per cent of all new AF cases, and 76% of cases aged ≥65 years, had a class-1 oral anticoagulation (OAC) recommendation (modified CHA2DS2-VASc score ≥2 men, ≥3 women). CONCLUSIONS: Repeated annual ECG screening of the same population provides a consistent yield of new AF each year. The majority of new AF (≥65 years) are eligible for anticoagulation for stroke prevention. Although AF prevalence and incidence are lower in Japan than Western countries, 2318 new cases would be identified in Toyama prefecture each year with annual screening, of whom ~927 would have a high stroke risk with a recommendation for OAC therapy.


Assuntos
Fibrilação Atrial/epidemiologia , Eletrocardiografia , Adulto , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Estudos de Coortes , Feminino , Humanos , Incidência , Japão , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/prevenção & controle
14.
Pediatr Int ; 51(4): 507-13, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19400815

RESUMO

BACKGROUND: Body image, defined here as an inaccurate perception of personal bodyweight, plays a significant role in the development of obesity, eating problems and eating disorders. Certain lifestyle factors may influence an individual's body image, but current knowledge is based mainly on studies in Western populations. METHODS: The associations between body image and lifestyle factors were investigated in samples of the Japanese female adolescent population. RESULTS: Respondents who reported that they ate meals slowly (odds ratio [OR] 1.81, P < 0.001) or only consumed small amounts of food (OR 3.17, P < 0.001) were more likely to underestimate their body image, as determined by their body mass index, than eaters who had average behavior for this age group. Individuals who reported eating faster (OR 1.47, P < 0.001) or consuming large amounts (OR 1.67, P < 0.001); those who do not eat breakfast on a daily basis (OR 1.35, P = 0.006); those who go to bed later than the average time for this age group (OR 1.38, P < 0.001) or sleep <7 h (OR 1.40, P < 0.001) and those individuals who rarely exercise (OR 1.27, P = 0.03) were more likely to overestimate their body image, as determined by BMI, compared with those who had average eating, sleeping and exercise behaviors for this age group. CONCLUSIONS: Variation from the norm in eating, sleeping and exercise behaviors showed a relationship with a distorted perception of body image in Japanese adolescent girls. These findings are of potential importance in understanding the underlying mechanisms involved in the development of body image and for exploring interventional approaches.


Assuntos
Imagem Corporal , Estilo de Vida , Adolescente , Estudos Transversais , Exercício Físico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Japão , Transtornos do Sono-Vigília/epidemiologia
15.
Hepatology ; 46(6): 1935-45, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17705296

RESUMO

UNLABELLED: Alternative methods to whole liver transplantation require a suitable cell that can be expanded to obtain sufficient numbers required for successful transplantation while maintaining the ability to differentiate into hepatocytes. Mesenchymal stem cells (MSCs) possess several advantageous characteristics for cell-based therapy and have been shown to be able to differentiate into hepatocytes. Thus, we investigated whether the intrahepatic delivery of human MSCs is a safe and effective method for generating human hepatocytes and whether the route of administration influences the levels of donor-derived hepatocytes and their pattern of distribution throughout the parenchyma of the recipient's liver. Human clonally derived MSCs were transplanted by an intraperitoneal (n = 6) or intrahepatic (n = 6) route into preimmune fetal sheep. The animals were analyzed 56-70 days after transplantation by immunohistochemistry, enzyme-linked immunosorbent assay, and flow cytometry. The intrahepatic injection of human MSCs was safe and resulted in more efficient generation of hepatocytes (12.5% +/- 3.5% versus 2.6% +/- 0.4%). The animals that received an intrahepatic injection exhibited a widespread distribution of hepatocytes throughout the liver parenchyma, whereas an intraperitoneal injection resulted in a preferential periportal distribution of human hepatocytes that produced higher amounts of albumin. Furthermore, hepatocytes were generated from MSCs without the need to first migrate/lodge to the bone marrow and give rise to hematopoietic cells. CONCLUSION: Our studies provide evidence that MSCs are a valuable source of cells for liver repair and regeneration and that, by the alteration of the site of injection, the generation of hepatocytes occurs in different hepatic zones, suggesting that a combined transplantation approach may be necessary to successfully repopulate the liver with these cells.


Assuntos
Hepatócitos/fisiologia , Regeneração Hepática/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Animais , Células Clonais , Feto , Hepatócitos/citologia , Humanos , Injeções , Injeções Intraperitoneais , Fígado , Ovinos , Transplante Heterólogo
16.
J Pediatr ; 151(5): 518-22, 522.e1-4, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17961698

RESUMO

OBJECTIVE: To examine daytime sleepiness and sleepiness interrelationship with sleep-wake patterns, eating habits, physical activity, and TV/video game time. STUDY DESIGN: A cross-sectional survey with 9,261 school children (mean age of 12.8 years) from 93 junior high schools in Toyama prefecture, Japan. RESULTS: The main outcome measures were daytime sleepiness during schooldays and sleepiness interrelationship with sleep-wake patterns, eating habits, physical activity, and visual media use. A total of 2,328 children (25.2%) reported sleepiness almost always and 4,401 (47.6%) sleepiness often. Regarding sex difference, a higher proportion of girls reported sleepiness in comparison to boys (79% vs 66%, P < .001). Higher body mass index values were associated with the presence of sleepiness. In girls with preferences for daily snack (versus those who reported no snack) sleepiness presented significantly (P < .001) higher values. Reduced sleep time was significantly associated with sleepiness. The prevalence of sleepiness did not significantly differ among groups who had 7.5 hours sleep or more. A dose-response relation was found between sleepiness and sleep disturbances, physical activity, and media use time. CONCLUSIONS: Sleep insufficiency represents a main cause for daytime sleepiness in Japanese junior high school children. Proper sleep habits, high physical activity level, and limited TV viewing time should be promoted among school children.


Assuntos
Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Atividade Motora , Privação do Sono , Televisão , Jogos de Vídeo , Adolescente , Índice de Massa Corporal , Criança , Estudos Transversais , Comportamento Alimentar , Feminino , Humanos , Japão/epidemiologia , Masculino , Fatores Sexuais , Inquéritos e Questionários
17.
Anal Sci ; 22(11): 1473-6, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17099282

RESUMO

Compared to generally used solvent extraction methods, supercritical fluid extraction (SFE) with carbon dioxide has the advantages of automation and simple operation in preparing samples for pesticide residue analysis. This report is the outcome of our evaluation of the practicality of SFE for the preparation of samples for pesticide residue analysis. We studied the recovery of 303 compounds with several crops by a simultaneous analytical method of SFE, cartridge column purification, followed by GC/MS determination. We achieved 70 to 120% recovery for more than 80% of the examined compounds.

18.
Int J Epidemiol ; 44(2): 405-14, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24872224

RESUMO

The Japanese Population-based Osteoporosis (JPOS) Cohort Study was launched in 1996 to produce a reference database of areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA) and bone turnover markers in the Japanese female population and to determine risk factors for osteoporotic fractures. At baseline, 3984 women aged 15 to 79 years were randomly selected to provide representative bone status data and aBMD values for the diagnosis of osteoporosis. Follow-up surveys were conducted in 1999, 2002, 2006 and 2011/12 to determine changes in aBMD and identify incident morphometry-confirmed vertebral fractures and clinical fractures. These outcomes were obtained from 2174 women who participated in at least one follow-up survey. JPOS is a unique resource of individual-level bone health information with radiological and biological archives that include DXA images, and serum, plasma and DNA for future analyses with emerging radiological and biological techniques. The JPOS dataset is not freely available, but new collaborations are encouraged. Potential collaborators are invited to contact the Secretary General (M.I.) at the administrative office of the JPOS Study Group.


Assuntos
Osteoporose/epidemiologia , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Densidade Óssea/fisiologia , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Vértebras Lombares , Pessoa de Meia-Idade , Osteoporose/fisiopatologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Valores de Referência , Características de Residência/estatística & dados numéricos , Fatores de Risco , Vértebras Torácicas , Adulto Jovem
19.
J Gastroenterol ; 37(12): 1068-72, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12522541

RESUMO

A 38-year-old Japanese woman with no past history of liver disease developed liver dysfunction associated with fever, anorexia, and general malaise following the prolonged administration of saridon. A liver biopsy demonstrated multiple noncaseating epithelioid granulomas within hepatic lobules, with an inflammatory cell infiltrate of the lobular parenchyma and portal tracts. Viral markers and autoantibodies were negative. Lymphocyte stimulation tests for saridon and for isopropylantipyrine, one of the constituents of saridon, were positive, and therefore a diagnosis of drug-induced hepatitis due to administration of saridon was made. Her symptoms resolved and liver function test results returned to normal following discontinuation of the drug. The possibility of drug-induced hepatitis must be considered when liver dysfunction or systemic symptomatology develops during saridon therapy.


Assuntos
Antipirina/análogos & derivados , Antipirina/efeitos adversos , Cafeína/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Granuloma/induzido quimicamente , Fenacetina/efeitos adversos , Piridonas/efeitos adversos , Adulto , Antipirina/uso terapêutico , Biópsia por Agulha , Cafeína/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Combinação de Medicamentos , Feminino , Seguimentos , Granuloma/complicações , Granuloma/patologia , Cefaleia/diagnóstico , Cefaleia/tratamento farmacológico , Humanos , Imuno-Histoquímica , Testes de Função Hepática , Fenacetina/uso terapêutico , Piridonas/uso terapêutico , Medição de Risco , Índice de Gravidade de Doença
20.
Anal Sci ; 28(7): 669-73, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22790368

RESUMO

Fenthion, fenthion sulfoxide, fenthion oxon sulfoxide and fensulfothion showed two different mass spectra in GC/MS, depending on their concentrations. The base peaks shifted to lower levels by 1 m/z at lower concentration, and no retention time shifts were observed. The "shifted base peaks" were not obtained by a general EI fragmentation. The product ion scan spectra of the "shifted base peaks" were coincident with those of molecular ions of their corresponding sulfides. These phenomena can be ascribed to the conversion of sulfoxide into sulfide by the dominant deoxidation reaction than EI fragmentation in an ion source. Adding polyethylene glycol 300 (PEG300) into a test solution prevented sulfoxide deoxidation.


Assuntos
Fention/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Organotiofosforados/química , Polietilenoglicóis/química , Safrol/análogos & derivados , Injeções , Oxirredução , Safrol/química , Solventes/química , Temperatura
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