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1.
Phys Rev Lett ; 120(20): 206402, 2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29864291

RESUMO

The spin states of Co^{3+} ions in perovskite-type LaCoO_{3}, governed by the complex interplay between the electron-lattice interactions and the strong electron correlations, still remain controversial due to the lack of experimental techniques which can directly detect them. In this Letter, we revealed the tensile-strain dependence of spin states, i.e., the ratio of the high- and low-spin states, in epitaxial thin films and a bulk crystal of LaCoO_{3} via resonant inelastic soft x-ray scattering. A tensile strain as small as 1.0% was found to realize different spin states from that in the bulk.

2.
Orthod Craniofac Res ; 20(2): 95-101, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28414873

RESUMO

OBJECTIVES: To examine the influence of negative pressure of the pharyngeal airway on mandibular retraction during inspiration in children with nasal obstruction using the computational fluid dynamics (CFD) method. SETTING AND SAMPLE POPULATION: Sixty-two children were divided into Classes I, II (mandibular retrusion) and III (mandibular protrusion) malocclusion groups. MATERIAL AND METHODS: Cone-beam computed tomography data were used to reconstruct three-dimensional shapes of the nasal and pharyngeal airways. Airflow pressure was simulated using CFD to calculate nasal resistance and pharyngeal airway pressure during inspiration and expiration. RESULTS: Nasal resistance of the Class II group was significantly higher than that of the other two groups, and oropharyngeal airway inspiration pressure in the Class II (-247.64 Pa) group was larger than that in the Class I (-43.51 Pa) and Class III (-31.81 Pa) groups (P<.001). The oropharyngeal airway inspiration-expiration pressure difference in the Class II (-27.38 Pa) group was larger than that in the Class I (-5.17 Pa) and Class III (0.68 Pa) groups (P=.006). CONCLUSION: Large negative inspiratory pharyngeal airway pressure due to nasal obstruction in children with Class II malocclusion may be related to their retrognathia.


Assuntos
Resistência das Vias Respiratórias , Tomografia Computadorizada de Feixe Cônico , Má Oclusão Classe II de Angle/diagnóstico por imagem , Má Oclusão Classe II de Angle/fisiopatologia , Obstrução Nasal/diagnóstico por imagem , Obstrução Nasal/fisiopatologia , Faringe/anormalidades , Faringe/diagnóstico por imagem , Criança , Feminino , Humanos , Masculino , Pressão
3.
J Oral Rehabil ; 43(8): 575-82, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27121170

RESUMO

We aimed to investigate mastication predominance in healthy dentate individuals and patients with unilateral posterior missing teeth using objective and subjective methods. The sample comprised 50 healthy dentate individuals (healthy dentate group) and 30 patients with unilateral posterior missing teeth (partially edentulous group). Subjects were asked to freely chew three kinds of test foods (peanuts, beef jerky and chewing gum). Electromyographic activity of the bilateral masseter muscles was recorded. The chewing side (right side or left side) was judged by the level of root mean square electromyographic amplitude. Mastication predominance was then objectively assessed using the mastication predominant score and the mastication predominant index. Self-awareness of mastication predominance was evaluated using a modified visual analogue scale. Mastication predominance scores of the healthy dentate and partially edentulous groups for each test food were analysed. There was a significant difference in the distribution of the mastication predominant index between the two groups (P < 0·05). The mastication predominant score was weakly correlated with self-awareness of mastication predominance in the healthy dentate group, whereas strong correlation was observed in the partially edentulous group (P < 0·05). The results suggest that the individuals with missing unilateral posterior teeth exhibited greater mastication predominance and were more aware of mastication predominance than healthy dentate individuals. Our findings suggest that an objective evaluation of mastication predominance is more precise than a subjective method.


Assuntos
Eletromiografia , Arcada Parcialmente Edêntula/fisiopatologia , Músculo Masseter/fisiologia , Mastigação/fisiologia , Adulto , Idoso , Goma de Mascar , Feminino , Alimentos , Voluntários Saudáveis , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Escala Visual Analógica , Adulto Jovem
4.
Clin Radiol ; 70(11): 1289-98, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26272529

RESUMO

AIM: To find significant parameters to characterise anterior mediastinal solid tumours in adults using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted MRI (DWI), and combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: Forty-eight histologically confirmed anterior mediastinal solid tumours in 48 patients (24 men, 24 women; age range 21-83 years, mean 50.7 years) were examined. The parameters analysed were maximal diameter, presence of capsule/septa on T2-weighted images, time-signal intensity curves (TICs), apparent diffusion coefficient (ADC), and maximum standardised uptake value (SUVmax). Also examined was whether any differences between histological types could be seen in these parameters. In a validation study, 42 anterior mediastinal solid tumours in 42 patients were examined consecutively. RESULTS: The washout pattern on TIC was seen only in thymic epithelial tumours (20/32). SUVmax of lymphoma (mean, 17.9), malignant germ cell tumours (14.2), and thymic carcinomas (15.6) were significantly higher than that of thymomas (6.1). The mean maximal diameter of thymic epithelial tumours was significantly smaller than that of lymphomas (p<0.01) and malignant germ cell tumours (p<0.05). The validation study also yielded high accuracy (38/42, 91%) in differentiation among the anterior mediastinal solid tumours. CONCLUSION: The SUVmax, TIC pattern on DCE-MRI, and maximal diameter might be useful to differentiate anterior mediastinal solid tumours in adults.


Assuntos
Neoplasias do Mediastino/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Fluordesoxiglucose F18 , Humanos , Linfoma/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Epiteliais e Glandulares/patologia , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Curva ROC , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Timoma/patologia , Neoplasias do Timo/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
5.
Phys Rev Lett ; 111(3): 037204, 2013 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-23909357

RESUMO

Both electric- and magnetic-dipole active spin excitations, i.e., electromagnons, which mediate the dynamical magnetoelectric effect, have been investigated for a multiferroic perovskite of manganite by optical spectroscopy at terahertz frequencies. Upon the magnetoelectric resonance at 1 meV in the multiferroic phase with the bc-plane spin cycloidal order, a gigantic dynamical magnetoelectric effect has been observed as a nonreciprocal directional dichroism or birefringence. The light k-vector-dependent difference (Δκ=κ(+)-κ(-)) of the extinction coefficient (κ(±)) is as large as Δκ~1 or 2Δκ/(κ(+)+κ(-))~0.7 at the lowest-lying electromagnon energy. We clarified the mutual coupling of the E(ω)[parallel]a-polarized electromagnons of the different origins, leading to the enhancement of the magnetoelectric resonance.

6.
Phys Rev Lett ; 111(2): 027206, 2013 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-23889438

RESUMO

We have investigated the Co-3d spin-orbital state in a thin film of perovskite LaCoO3 to clarify the origin of strain induced spontaneous magnetization (T(C)=94 K) by means of x-ray diffraction, optical spectroscopy, and magnetization measurements. A lattice distortion with the propagation vector (1/4 -1/4 1/4) and an anomalous activation of optical phonons coupled to Co-3d orbital are observed below 126 K. Combined with the azimuthal angle analysis of superlattice reflection, we propose that the ordering of Co-3d orbital promoted by an epitaxial strain produces a unique ferrimagnetic structure.

8.
Nat Genet ; 22(1): 27-36, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10319858

RESUMO

A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping.


Assuntos
Marcadores Genéticos/genética , Genoma , Ratos/genética , Animais , Mapeamento Cromossômico , Cromossomos/genética , Genes/genética , Humanos , Células Híbridas , Camundongos , Dados de Sequência Molecular
9.
Phys Rev Lett ; 108(4): 047203, 2012 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-22400885

RESUMO

We investigated the magnetic structure of an orthorhombic YMnO(3) thin film by resonant soft x-ray and hard x-ray diffraction. We observed a temperature-dependent incommensurate magnetic reflection below 45 K and a commensurate lattice-distortion reflection below 35 K. These results demonstrate that the ground state is composed of coexisting E-type and cycloidal states. Their different ordering temperatures clarify the origin of the large polarization to be caused by the E-type antiferromagnetic states in the orthorhombic YMnO(3) thin film.

10.
Diabetologia ; 53(3): 419-28, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20054522

RESUMO

AIMS/HYPOTHESIS: The aim of the study was to clarify whether a therapeutic intervention focused on lifestyle modification affected the incidence of vascular complications in patients with established diabetes. METHODS: A total of 2,033 eligible Japanese men and women aged 40-70 years with type 2 diabetes from 59 institutes were randomised to a conventional treatment group (CON), which continued to receive the usual care, and a lifestyle intervention group (INT), which received education on lifestyle modification regarding dietary habits, physical activities and adherence to treatment by telephone counselling and at each outpatient clinic visit, in addition to the usual care. Randomisation and open-label allocation were done by a central computer system. Primary analysis regarding measurements of control status and occurrence of macro- and microvascular complications was based on 1,304 participants followed for an 8 year period. RESULTS: Although status of control of most classic cardiovascular risk factors, including body weight, glycaemia, serum lipids and BP, did not differ between groups during the study period, the incidence of stroke in the INT group (5.48/1,000 patient-years) was significantly lower than in the CON group (9.52/1,000 patient-years) by Kaplan- Meier analysis (p=0.02 by logrank test) and by multivariate Cox analysis (HR 0.62, 95% CI 0.39-0.98, p=0.04). The incidence of CHD, retinopathy and nephropathy did not differ significantly between groups. Lipoprotein(a) was another significant independent risk factor for stroke. CONCLUSIONS/INTERPRETATION: These findings suggest that lifestyle modification had limited effects on most typical control variables, but did have a significant effect on stroke incidence in patients with established type 2 diabetes. CLINICAL TRIAL REGISTRATION: UMIN-CTR C000000222 FUNDING: The Ministry of Health, Labour and Welfare, Japan


Assuntos
Diabetes Mellitus Tipo 2/terapia , Estilo de Vida , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Complicações do Diabetes , Dieta , Feminino , Humanos , Incidência , Japão , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento
11.
J Oral Rehabil ; 37(1): 26-33, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19874450

RESUMO

The purpose of this study was to clarify whether the reverse cycle during chewing is abnormal in children with primary dentition. Children with normal primary dentition (N = 23; 5.5 +/- 0.8 years) and female adults (N = 25; 20.7 +/- 1.9 years) participated in this study. Chewing movement was recorded using an opto-electronic analysis system with six degrees-of-freedom (TRI-MET, Tokyo-shizaisha; Tokyo, Japan). Each subject was given a stick of chewing gum (new TRIDENT, WARNER-LAMBERT CO., Morris Plains, NJ, USA) and instructed to chew it normally. Starting from the maximum intercuspal position, each chewing sequence was recorded over a period of 20 s. A custom computer program identified individual chewing cycles. Frontal views were used to distinguish seven types of cycle shapes according to Ahlgren (Acta Odontol Scand, 24, 1966, 1-109; Acta Odontol Scand, 25, 1967, 3-13). Multilevel statistical models evaluated differences between children and adults. In the adults, type II cycles that initially opened towards the balancing side and then moved towards the working side were the most common, and the closing pathway was lateral to the opening pathway. In the children, type V (reverse) cycles that opened towards the working side were most common, the closing pathway was medial to the opening pathway, and there was a smaller lateral component during opening and closing than in adults (P < 0.05). We conclude that the reverse cycle is not abnormal because normal children with primary dentition have a smaller lateral component and difficulty in controlling asymmetric muscle activity.


Assuntos
Oclusão Dentária , Mastigação/fisiologia , Amplitude de Movimento Articular , Articulação Temporomandibular/fisiologia , Dente Decíduo , Fatores Etários , Goma de Mascar , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mandíbula , Movimento/fisiologia , Oscilometria , Valores de Referência , Adulto Jovem
12.
Sci Rep ; 10(1): 18596, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122696

RESUMO

Topological magnetic structure possesses topological stability characteristics that make it robust against disturbances which are a big advantage for data processing or storage devices of spintronics; nonetheless, such characteristics have been rarely clarified. This paper focused on the formation of chiral soliton lattice (CSL), a one-dimensional topological magnetic structure, and provides a discussion of its topological stability and influence of thermal fluctuation. Herein, CSL responses against change of temperature and applied magnetic field were investigated via small-angle resonant soft X-ray scattering in chromium niobium sulfide ([Formula: see text]). CSL transformation relative to the applied magnetic field demonstrated a clear agreement with the theoretical prediction of the sine-Gordon model. Further, there were apparent differences in the process of chiral soliton creation and annihilation, discussed from the viewpoint of competing between thermal fluctuation and the topological metastability.

13.
Nat Commun ; 11(1): 5685, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177528

RESUMO

Magnetic skyrmion is a topologically protected particle-like object in magnetic materials, appearing as a nanometric swirling spin texture. The size and shape of skyrmion particles can be flexibly controlled by external stimuli, which suggests unique features of their crystallization and lattice transformation process. Here, we investigated the detailed mechanism of structural transition of skyrmion lattice (SkL) in a prototype chiral cubic magnet Cu2OSeO3, by combining resonant soft X-ray scattering (RSXS) experiment and micromagnetic simulation. This compound is found to undergo a triangular-to-square lattice transformation of metastable skyrmions by sweeping magnetic field (B). Our simulation suggests that the symmetry change of metastable SkL is mainly triggered by the B-induced modification of skyrmion core diameter and associated energy cost at the skyrmion-skyrmion interface region. Such internal deformation of skyrmion particle has further been confirmed by probing the higher harmonics in the RSXS pattern. These results demonstrate that the size/shape degree of freedom of skyrmion particle is an important factor to determine their stable lattice form, revealing the exotic manner of phase transition process for topological soliton ensembles in the non-equilibrium condition.

14.
Biochem Biophys Res Commun ; 379(4): 861-5, 2009 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-19126404

RESUMO

It is well known that oxidative stress plays critical roles in the pathogenesis of atherosclerosis. In this study, we enrolled 1746 type 2 diabetic subjects, determined 4 common genetic variants related to oxidative stress (glutamate-cysteine ligase modifier subunit (GCLM) C-588T, myeloperoxidase G-463A, human paraoxonase 1 Gln192Arg and NAD(P)H oxidase p22phox C242T polymorphisms), and measured carotid intima-media thickness (IMT) as a surrogate marker for atherosclerosis. GCLM C-588T polymorphism was associated with average IMT (AveIMT) (r=0.090, p=0.0008), but the association between the other 3 polymorphisms and AveIMT did not reach the statistical significance. However, AveIMT was significantly greater as the total number of 4 concomitant "pro-oxidant alleles" in each subject was increased (r=0.108, p<0.0001). Furthermore, the number of "pro-oxidant alleles" was a risk factor for a high AveIMT independently of conventional risk factors (p=0.0003). In conclusion, accumulation of oxidative stress-associated alleles was associated with carotid atherosclerosis in type 2 diabetic patients.


Assuntos
Aterosclerose/genética , Doenças das Artérias Carótidas/genética , Predisposição Genética para Doença , Estresse Oxidativo/genética , Polimorfismo Genético , Alelos , Arildialquilfosfatase/genética , Aterosclerose/complicações , Aterosclerose/patologia , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/enzimologia , Feminino , Glutamato-Cisteína Ligase/genética , Humanos , Masculino , Peroxidase/genética , Túnica Íntima/patologia
15.
Phys Rev Lett ; 103(18): 187202, 2009 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-19905827

RESUMO

Magnetic and dielectric properties of Eu1-xYxMnO3 (x=0 and 0.4) are studied in pulsed magnetic fields up to 55 T. For x=0, application of magnetic fields higher than 20 T along the b axis causes magnetic transitions accompanied by generation of electric polarization (P) along the a axis. Similar first-order transitions are also observed in crystals of x=0.4, in which the ground state at zero magnetic field is already a ferroelectric P parallel a phase of different origin. Realistic model calculation indicates the presence of a novel multiferroic state induced by the spin exchange striction mechanism in high magnetic fields as an essential nature of the frustrated Mn spin system in this class of manganites.

16.
J Vet Intern Med ; 32(1): 165-171, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29356095

RESUMO

BACKGROUND: In veterinary medicine, congenital methemoglobinemia associated with nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) deficiency is rare. It has been reported in several breeds of dogs, but little information is available about its etiology. OBJECTIVES: To analyze the NADH-cytochrome b5 reductase gene, CYB5R3, in a Pomeranian dog family with methemoglobinemia suspected to be caused by congenital b5R deficiency. ANIMALS: Three Pomeranian dogs from a family with methemoglobinemia were analyzed. Five healthy beagles and 5 nonrelated Pomeranian dogs without methemoglobinemia were used as controls. METHODS: Methemoglobin concentration, b5R activity, and reduced glutathione (GSH) concentration were measured, and a turbidity index was used to evaluate Heinz body formation. The CYB5R3 genes of the affected dog and healthy dogs were analyzed by direct sequencing. RESULTS: Methemoglobin concentrations in erythrocytes of the affected dogs were remarkably higher than those of the control dogs. The b5R activity of the affected dogs was notably lower than that of the control dogs. DNA sequencing indicated that this Pomeranian family carried a CYB5R3 gene missense variant (ATC→CTC at codon 194) that resulted in the replacement of isoleucine (Ile) by leucine (Leu). CONCLUSIONS AND CLINICAL IMPORTANCE: This dog family had familial congenital methemoglobinemia caused by b5R deficiency, which resulted from a nonsynonymous variant in the CYB5R3 gene. This variation (c.580A>C) led to an amino acid substitution (p.Ile194Leu), and Ile194 was located in the proximal region of the NADH-binding motif. Our data suggested that this variant in the canine CYB5R3 gene would affect function of the b5R in erythrocytes.


Assuntos
Citocromo-B(5) Redutase/deficiência , Citocromo-B(5) Redutase/genética , Doenças do Cão/genética , Metemoglobinemia/congênito , Mutação de Sentido Incorreto , Animais , Doenças do Cão/sangue , Cães , Feminino , Glutationa/sangue , Corpos de Heinz , Masculino , Metemoglobinemia/genética , Metemoglobinemia/veterinária , Análise de Sequência de DNA
17.
J Clin Invest ; 100(7): 1840-6, 1997 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-9312185

RESUMO

The insulin gene transcription factor PDX-1/IPF1/STF-1/ IDX-1 plays a key role in directing beta cell-specific gene expressions. Recently, impairment of PDX-1 expression or activity has been observed in beta cell-derived HIT cells cultured under high glucose concentrations, and this has been suggested as a possible cause of the decrease in insulin gene transcription. To investigate the pathophysiological significance of PDX-1 as a determinant of the rate of insulin gene transcription, we suppressed its expression in beta cell-derived MIN6 cells using an antisense oligodeoxynucleotide (ODN) and searched for possible changes in the beta cell-specific gene expression. Treatment of MIN6 cells with an 18-mer phosphorothioate ODN complementary to a sequence starting at the translation initiation codon of PDX-1 caused a potent, concentration-dependent reduction in PDX-1 expression; addition of 2 microM antisense ODN could reduce PDX-1 expression to 14+/-4% of the control. There was also a decrease in its DNA binding to the insulin gene A element. Despite such suppression of PDX-1, Northern blot analysis revealed no decrease in the amount of insulin mRNA in the MIN6 cells. Similarly, no changes were detected in the transcription of the glucokinase or islet amyloid polypeptide gene, for which PDX-1 was shown to function as a transcription factor. Thus, our findings dispute the physiological significance of PDX-1 in determining the rate of insulin gene transcription. This means that other components constituting the transcription-controlling machinery need to be evaluated in order to understand the molecular basis of impaired insulin biosynthesis such as that observed due to glucose toxicity.


Assuntos
Regulação da Expressão Gênica , Proteínas de Homeodomínio , Insulina/biossíntese , Ilhotas Pancreáticas/metabolismo , Transativadores/genética , Sítios de Ligação , Linhagem Celular , Expressão Gênica , Glucose/farmacologia , Insulina/genética , Ilhotas Pancreáticas/citologia , Oligonucleotídeos Antissenso/farmacologia , Ligação Proteica , RNA Mensageiro/análise , Sequências Reguladoras de Ácido Nucleico , Supressão Genética , Transcrição Gênica
18.
J Clin Invest ; 99(1): 144-50, 1997 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-9011569

RESUMO

Prolonged poor glycemic control in non-insulin-dependent diabetes mellitus patients often leads to a decline in insulin secretion from pancreatic beta cells, accompanied by a decrease in the insulin content of the cells. As a step toward elucidating the pathophysiological background of the so-called glucose toxicity to pancreatic beta cells, we induced glycation in HIT-T15 cells using a sugar with strong deoxidizing activity, D-ribose, and examined the effects on insulin gene transcription. The results of reporter gene analyses revealed that the insulin gene promoter is more sensitive to glycation than the control beta-actin gene promoter; approximately 50 and 80% of the insulin gene promoter activity was lost when the cells were kept for 3 d in the presence of 40 and 60 mM D-ribose, respectively. In agreement with this, decrease in the insulin mRNA and insulin content was observed in the glycation-induced cells. Also, gel mobility shift analyses using specific antiserum revealed decrease in the DNA-binding activity of an insulin gene transcription factor, PDX-1/IPF1/STF-1. These effects of D-ribose seemed almost irreversible but could be prevented by addition of 1 mM aminoguanidine or 10 mM N-acetylcysteine, thus suggesting that glycation and reactive oxygen species, generated through the glycation reaction, serve as mediators of the phenomena. These observations suggest that protein glycation in pancreatic beta cells, which occurs in vivo under chronic hyperglycemia, suppresses insulin gene transcription and thus can explain part of the beta cell glucose toxicity.


Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Produtos Finais de Glicação Avançada/genética , Produtos Finais de Glicação Avançada/metabolismo , Proteínas de Homeodomínio , Insulina/genética , Insulina/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos , Ribose/farmacologia , Acetilcisteína/farmacologia , Linfócitos B , Northern Blotting , Células Cultivadas , Clonagem Molecular , Genes Reporter , Glucose/toxicidade , Guanidinas/farmacologia , Humanos , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Ribose/antagonistas & inibidores , Transativadores/genética , Transativadores/fisiologia , Transcrição Gênica
19.
Neuroscience ; 145(2): 520-9, 2007 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-17241746

RESUMO

Hematopoietic prostaglandin D synthase is a key enzyme in synthesis of prostaglandin D. Hematopoietic prostaglandin D synthase is expressed in microglia of the developing mouse brain. This study determined the serial changes and cellular localization of hematopoietic prostaglandin D synthase, and its role in cerebral ischemia/reperfusion injury using C57BL/6 mice (n=84) and bone marrow chimera mice (n=16). The latter mice were selected based on their expression of enhanced green fluorescent protein in bone marrow/blood-derived monocytes/macrophages. The middle cerebral artery was occluded for 60 min, followed by reperfusion. Hematopoietic prostaglandin D synthase expression was examined by immunohistochemistry and Western blotting. Hematopoietic prostaglandin D synthase-positive cells were mainly expressed in the peri-ischemic area at 12 h (P<0.05) and 24 h (P<0.001) after reperfusion, while they were mostly found in the transition area at 48-72 h postreperfusion (P<0.001). There was a significant increase in staining intensity as well as number of hematopoietic prostaglandin D synthase-positive cells in the ischemic core at 5-7 (P<0.001) days postreperfusion. Hematopoietic prostaglandin D synthase-positive cells also co-expressed ionized calcium-binding adapter molecule 1, a marker of microglia/macrophages, and cyclooxygenase-2, but not markers of neurons, oligodendrocytes and astrocytes. Until 72 h postreperfusion, many enhanced green fluorescent protein-positive cells were negative for hematopoietic prostaglandin D synthase, but the number of hematopoietic prostaglandin D synthase-enhanced green fluorescent protein coexpressing cells increased significantly at 5-7 days after reperfusion. Our results indicate that hematopoietic prostaglandin D synthase is mainly produced by endogenous microglia until 72 h after reperfusion, but at 7 days after reperfusion, it is also produced by migrating bone marrow/blood-derived macrophages in the ischemic brain tissue. We speculate that hematopoietic prostaglandin D synthase in the brain has different functions during early and late phases of ischemia.


Assuntos
Isquemia Encefálica/enzimologia , Encéfalo/enzimologia , Oxirredutases Intramoleculares/metabolismo , Macrófagos/enzimologia , Microglia/enzimologia , Traumatismo por Reperfusão/enzimologia , Animais , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Isquemia Encefálica/fisiopatologia , Proteínas de Ligação ao Cálcio/metabolismo , Contagem de Células , Movimento Celular/fisiologia , Proliferação de Células , Ciclo-Oxigenase 2/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hematopoese/fisiologia , Lipocalinas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos , Prostaglandina D2/biossíntese , Traumatismo por Reperfusão/fisiopatologia , Quimeras de Transplante , Regulação para Cima
20.
Mol Cell Biol ; 19(12): 8281-91, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10567553

RESUMO

Pax4 is a paired-domain (PD)-containing transcription factor which plays a crucial role in pancreatic beta/delta-cell development. In this study, we characterized the DNA-binding and transactivation properties of mouse Pax4. Repetitive rounds of PCR-based selection led to identification of the optimal DNA-binding sequences for the PD of Pax4. In agreement with the conservation of the optimal binding sequences among the Pax family transcription factors, Pax4 could bind to the potential binding sites for Pax6, another member of the Pax family also involved in endocrine pancreas development. The overexpression of Pax4 in HIT-T15 cells dose dependently inhibited the basal transcriptional activity as well as Pax6-induced activity. Detailed domain mapping analyses using GAL4-Pax4 chimeras revealed that the C-terminal region of Pax4 contains both activation and repression domains. The activation domain was active in the embryonic kidney-derived 293/293T cells and embryonal carcinoma-derived F9 cells, containing adenoviral E1A protein or E1A-like activity, respectively but was inactive or very weakly active in other cells including those of pancreatic beta- and alpha-cell origin. Indeed, the exogenous overexpression of type 13S E1A in heterologous cell types could convert the activation domain to an active one. On the other hand, the repression domain was active regardless of the cell type. When the repression domain was linked to the transactivation domain of a heterologous transcription factor, PDX-1, it could completely abolish the transactivation potential of PDX-1. These observations suggest a primary role of Pax4 as a transcriptional repressor whose function may involve the competitive inhibition of Pax6 function. The identification of the E1A-responsive transactivation domain, however, indicates that the function of Pax4 is subject to posttranslational regulation, providing further support for the complexity of mechanisms that regulate pancreas development.


Assuntos
Proteínas E1A de Adenovirus/metabolismo , Proteínas de Homeodomínio/fisiologia , Pâncreas/fisiologia , Proteínas Repressoras/fisiologia , Fatores de Transcrição/fisiologia , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Linhagem Celular Transformada , Cricetinae , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Ilhotas Pancreáticas/citologia , Camundongos , Dados de Sequência Molecular , Fatores de Transcrição Box Pareados , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Elementos de Resposta , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional
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