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1.
Artigo em Inglês | MEDLINE | ID: mdl-38083263

RESUMO

Glucose is essential as the main energy source for living organisms. However, excessive elevation of blood sugar levels can lead to diabetes and serious complications such as arteriosclerosis. Even though blood sugar levels as well as hypoxia associated with hyperglycemia are known to be closely related to diabetes complications, the responses of vascular endothelial cells to glucose and oxygen have not been fully investigated. In this study, using a microfluidic device that can control the oxygen concentration, we observed the behavior of vascular endothelial cell monolayers while simultaneously controlling glucose and oxygen levels. Results showed that the cell migration speed was increased by high-glucose exposure in an oxygen-rich environment, but was decreased in a hypoxic environment regardless of glucose condition. The expression of vascular endothelial-cadherin at the cell periphery, which plays a role in cell-cell adhesion, was increased by hypoxic exposure, but was largely independent of glucose condition. This suggested that cell-cell adhesion is less involved in the increase in migration caused by high glucose. Furthermore, stabilization and nuclear translocation of hypoxia-inducible factor-1α, which is involved in cellular hypoxia sensing, increased 5 h after exposure to high glucose, but decreased 3 days after the exposure. This indicated that intracellular hypoxia was generated by increased oxygen consumption in mitochondria just after the high-glucose exposure, but it was moderated within 3 days.


Assuntos
Glucose , Oxigênio , Humanos , Oxigênio/metabolismo , Glucose/farmacologia , Glucose/metabolismo , Células Endoteliais/metabolismo , Glicemia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Hipóxia , Movimento Celular
2.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 1187-1190, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34891499

RESUMO

Although spatiotemporal changes of oxygen in a microenvironment are known to affect the cellular dynamics of various eukaryotes, the details are not fully understood. Here, we describe the aerotaxis and aerokinesis of Dictyostelium discoideum (Dd), which has long been employed as a model organism for eukaryotic cells. We developed a microfluidic device capable of time-lapse observation of cultured cells while controlling oxygen concentrations in microchannels. Migratory behaviors of Dd were observed and quantitatively evaluated under an oxygen concentration gradient from 0% to 21% O2, as well as in various uniform oxygen conditions. In a hypoxic region within the oxygen concentration gradient, Dd migrated toward regions of higher oxygen concentration at increased velocity, which was independent of cell density. Observed under uniform oxygen concentrations of 1%, 2%, 3%, and 21%, the migration velocity of Dd increased significantly in hypoxic environments of 2% O2 or less. Thus, Dd shows aerotaxis, directed by the oxygen concentration gradient, and simultaneously shows aerokinesis, changing the migration velocity according to the oxygen concentration itself.


Assuntos
Dictyostelium , Linhagem Celular , Células Cultivadas , Quimiotaxia , Oxigênio
3.
Science ; 370(6512): 125-129, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33004522

RESUMO

Cooling devices based on caloric materials have emerged as promising candidates to become the next generation of coolers. Several electrocaloric (EC) heat exchangers have been proposed that use different mechanisms and working principles. However, a prototype that demonstrates a competitive temperature span has been missing. We developed a parallel-plate active EC regenerator based on lead scandium tantalate multilayer capacitors. After optimizing the structural design by using finite element modeling for guidance and to considerably improve insulation, we measured a maximum temperature span of 13.0 kelvin. This temperature span breaks a crucial barrier and confirms that EC materials are promising candidates for cooling applications.

5.
Nat Commun ; 11(1): 4582, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917897

RESUMO

Ferroaxial materials that exhibit spontaneous ordering of a rotational structural distortion with an axial vector symmetry have gained growing interest, motivated by recent extensive studies on ferroic materials. As in conventional ferroics (e.g., ferroelectrics and ferromagnetics), domain states will be present in the ferroaxial materials. However, the observation of ferroaxial domains is non-trivial due to the nature of the order parameter, which is invariant under both time-reversal and space-inversion operations. Here we propose that NiTiO3 is an order-disorder type ferroaxial material, and spatially resolve its ferroaxial domains by using linear electrogyration effect: optical rotation in proportion to an applied electric field. To detect small signals of electrogyration (order of 10-5 deg V-1), we adopt a recently developed difference image-sensing technique. Furthermore, the ferroaxial domains are confirmed on nano-scale spatial resolution with a combined use of scanning transmission electron microscopy and convergent-beam electron diffraction. Our success of the domain visualization will promote the study of ferroaxial materials as a new ferroic state of matter.

6.
Ultrasound Obstet Gynecol ; 55(6): 730-739, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31273862

RESUMO

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). RESULTS: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. CONCLUSIONS: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Curvas de aprendizaje del cierre de la espina bífida fetal mediante cirugía abierta y endoscópica: revisión sistemática y metaanálisis OBJETIVO: El ensayo del Estudio sobre la Gestión del Mielomeningocele (MOMS, por sus siglas en inglés) demostró la seguridad y eficacia de la cirugía fetal abierta para la espina bífida aperta (EBA). Las técnicas alternativas recientemente desarrolladas pueden reducir los riesgos de la madre sin comprometer los efectos neuroprotectores del feto. El objetivo de esta revisión sistemática fue evaluar la curva de aprendizaje (CA) de diferentes técnicas de cierre de la EBA fetal. MÉTODOS: Se realizaron búsquedas en las bases de datos de MEDLINE, Web of Science, EMBASE, Scopus y Cochrane, así como en la literatura gris, para identificar artículos relevantes sobre cirugía fetal para la EBA, sin restricción de idioma, publicados entre enero de 1980 y octubre de 2018. Se examinaron sistemáticamente los estudios identificados y se seleccionaron los que informaban de todos los procedimientos consecutivos y con seguimiento postnatal ≥12 meses. Los estudios se incluyeron sólo si informaban sobre las variables de resultado necesarias para medir la CA, definidas por la seguridad y la eficacia para el feto. Dos autores recuperaron los datos de forma independiente, evaluaron la calidad de los estudios y clasificaron las observaciones en bloques de 30 pacientes. Para el metaanálisis, los datos se agruparon mediante un modelo de efectos aleatorios cuando fueron heterogéneos. Para medir la CA, se usaron dos métodos complementarios. En el método de división de grupos, la competencia se definió cuando el procedimiento proporcionó resultados comparables a los del ensayo MOMS para 12 variables de resultados que representaban el resultado quirúrgico inmediato, la neuroprotección neonatal a corto plazo y la neuroprotección a largo plazo a ≥12 meses de edad. Luego, cuando se dispuso de los datos brutos de los pacientes, se realizó un análisis de suma acumulada basado en un resultado binario compuesto que definió el éxito de la cirugía. El resultado compuesto combinó cuatro variables clínicamente relevantes en cuanto a la seguridad (ausencia de parto pretérmino extremo <30 semanas; ausencia de muerte fetal a ≤7 días después de la cirugía) y eficacia (reducción de la hernia del rombencéfalo y ausencia de cualquier tratamiento neonatal de dehiscencia o derrame de líquido cefalorraquídeo en el lugar del cierre). RESULTADOS: De los 6024 resultados de la búsqueda, se incluyeron 17 (0,3%) estudios, todos ellos con un riesgo de sesgo bajo, moderado o incierto. El cierre de la EBA fetal se realizó mediante histerotomía estándar (11 estudios), mini histerotomía (un estudio) o fetoscopia, ya fuera mediante el cierre exteriorizado del útero de una sola capa (un estudio), el cierre percutáneo de una sola capa (tres estudios) o el cierre percutáneo de dos capas (un estudio). Sólo se pudieron metaanalizar los resultados de la histerotomía estándar. En general, los resultados mejoraron significativamente con la experiencia. Se alcanzó la competencia después de 35 casos consecutivos para la histerotomía estándar y se predijo que se alcanzaría después de ≥57 casos para la mini histerotomía y ≥56 para la fetoscopia percutánea de dos capas. En el caso de las fetoscopias percutánea y exteriorizada del útero de una sola capa, no se alcanzó la competencia en los 81 y 28 casos disponibles para el análisis, respectivamente, y no se pudo realizar el análisis de predicción de la CA. CONCLUSIONES: El número de casos operados está correlacionado con el resultado del cierre de la EBA fetal, y el número de casos operados necesarios para alcanzar la competencia estuvo entre 35 para la histerotomía estándar y ≥56-57 para las operaciones con mínima agresividad. Las observaciones realizadas proporcionan información importante para las instituciones que buscan establecer un nuevo centro fetal, desarrollar una nueva técnica de cirugía fetal o entrenar a su equipo, e informar a los médicos que remiten a especialistas a los posibles pacientes y a terceros. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Fetoscopia/educação , Feto/cirurgia , Histerotomia/educação , Espinha Bífida Cística/cirurgia , Adulto , Feminino , Humanos , Curva de Aprendizado , Gravidez , Espinha Bífida Cística/embriologia
7.
Nature ; 575(7783): 468-472, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31597164

RESUMO

Heat pumps based on magnetocaloric and electrocaloric working bodies-in which entropic phase transitions are driven by changes of magnetic and electric field, respectively-use displaceable fluids to establish relatively large temperature spans between loads to be cooled and heat sinks1,2. However, the performance of prototypes is limited because practical magnetocaloric working bodies driven by permanent magnets3-5 and electrocaloric working bodies driven by voltage6-16 display temperature changes of less than 3 kelvin. Here we show that high-quality multilayer capacitors of PbSc0.5Ta0.5O3 display large electrocaloric effects over a wide range of starting temperatures when the first-order ferroelectric phase transition is driven supercritically (as verified by Landau theory) above the Curie temperature of 290 kelvin by electric fields of 29.0 volts per micrometre. Changes of temperature in the large central area of the capacitor peak at 5.5 kelvin near room temperature and exceed 3 kelvin for starting temperatures that span 176 kelvin (complete thermalization would reduce these values from 5.5 to 3.3 kelvin and from 176 to 73 kelvin). If magnetocaloric working bodies were to be replaced with multilayer capacitors of PbSc0.5Ta0.5O3, then the established design principles behind magnetocaloric heat pumps could be repurposed for better performance without bulky and expensive permanent magnets.

8.
Phys Rev Lett ; 118(21): 211801, 2017 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-28598663

RESUMO

We report the first measurement of the τ lepton polarization P_{τ}(D^{*}) in the decay B[over ¯]→D^{*}τ^{-}ν[over ¯]_{τ} as well as a new measurement of the ratio of the branching fractions R(D^{*})=B(B[over ¯]→D^{*}τ^{-}ν[over ¯]_{τ})/B(B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ}), where ℓ^{-} denotes an electron or a muon, and the τ is reconstructed in the modes τ^{-}→π^{-}ν_{τ} and τ^{-}→ρ^{-}ν_{τ}. We use the full data sample of 772×10^{6} BB[over ¯] pairs recorded with the Belle detector at the KEKB electron-positron collider. Our results, P_{τ}(D^{*})=-0.38±0.51(stat)_{-0.16}^{+0.21}(syst) and R(D^{*})=0.270±0.035(stat)_{-0.025}^{+0.028}(syst), are consistent with the theoretical predictions of the standard model.

9.
Clin Genet ; 92(6): 654-658, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28477354

RESUMO

Epilepsy of infancy with migrating focal seizures (EIMFS) is an infantile epileptic encephalopathy characterized by refractory seizures, severe psychomotor delay, and multiple moving epileptic discharges. The genetic etiology of EIMFS is relatively homogeneous with the majority of causative mutations found in KCNT1. Currently, gene panel or whole-exome sequencing is used for testing. To verify the pathogenicity of a variant, co-segregation of the variant and the disorder in a pedigree is important; hence, de novo mutations that are judged to be deleterious may be considered pathogenic because the patients are isolated. In contrast, in cases from non-consanguineous families, genes that cause disorders in a recessive manner should remain as potential candidates. Herein, we performed gene panel sequencing of a patient with EIMFS from a non-consanguineous family, and found a compound heterozygous constellation consisting of a maternally inherited p.Ser399Leu and a de novo p.Arg880Leu in SLC12A5, which encodes the neuronal KCC2 cotransporter. These unique mutations show gene variants that act in a recessive manner may be pathogenic for patients from non-consanguineous families.


Assuntos
Epilepsias Mioclônicas/genética , Mutação de Sentido Incorreto , Convulsões/genética , Simportadores/genética , Criança , Eletroencefalografia , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/fisiopatologia , Expressão Gênica , Genes Recessivos , Heterozigoto , Humanos , Masculino , Herança Materna , Linhagem , Convulsões/diagnóstico , Convulsões/fisiopatologia , Simportadores/metabolismo
10.
J Appl Microbiol ; 120(3): 781-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26669704

RESUMO

AIMS: To elucidate an entry site of staphylococcal enterotoxin A (SEA), which is a major toxin for staphylococcal foodborne poisoning, into gastrointestinal tissue using a house musk shrew model. METHODS AND RESULTS: House musk shrews were per orally administered with recombinant SEA and localization of SEA in gastrointestinal tissues was investigated by immunohistochemistry and immunoelectron microscopy 30 min after administration. SEA was detected in a subset of intestinal epithelial cells and lamina propria in the villi of jejunum and ileum. This observation was also found in gastrointestinal loops. Morphological characteristics of the SEA-immunopositive cells indicated that goblet cells are an entry site of SEA.SEA entered mucus-expelling goblet cells and the induction of mucus secretion by alyll isothiocyanate resulted in an intensive SEA signal. These results suggest that mucus secretion by goblet cells is important for the translocation of SEA. CONCLUSIONS: SEA can translocate across intestinal epithelia via mucus-expelling goblet cells. SIGNIFICANCE AND IMPACTS OF THE STUDY: An entry site of SEA during translocation across the gastrointestinal mucosal barrier was investigated. This study was the first to demonstrate the significance of goblet cells as an entry site of this bacterial toxin.


Assuntos
Enterotoxinas/metabolismo , Células Caliciformes/metabolismo , Musaranhos , Infecções Estafilocócicas/microbiologia , Staphylococcus/metabolismo , Animais , Transporte Biológico , Modelos Animais de Doenças , Humanos , Mucosa Intestinal/metabolismo , Musaranhos/microbiologia , Infecções Estafilocócicas/metabolismo
11.
Phys Rev Lett ; 114(23): 232501, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26196794

RESUMO

At the Mainz Microtron MAMI, the first high-resolution pion spectroscopy from decays of strange systems was performed by electron scattering off a (9)Be target in order to study the Λ binding energy of light hypernuclei. Positively charged kaons were detected by a short-orbit spectrometer with a broad momentum acceptance at 0° forward angles with respect to the beam, efficiently tagging the production of strangeness in the target nucleus. Coincidentally, negatively charged decay pions were detected by two independent high-resolution spectrometers. About 10(3) pionic weak decays of hyperfragments and hyperons were observed. The pion momentum distribution shows a monochromatic peak at pπ≈133 MeV/c, corresponding to the unique signature for the two-body decay of hyperhydrogen Λ(4)H→(4)He+π(-), stopped inside the target. Its Λ binding energy was determined to be BΛ=2.12±0.01 (stat)±0.09 (syst)MeV with respect to the (3)H+Λ mass.

12.
J Pediatr Surg ; 50(4): 515-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25840053

RESUMO

BACKGROUND/PURPOSE: Congenital pulmonary airway malformations (CPAMs) are rare congenital lung lesions often diagnosed by prenatal ultrasound. High-risk cases can result in hydrops and prenatal or postnatal demise. Antenatal betamethasone has resulted in improved survival but it is unclear how to manage patients who do not respond to a single course. METHODS: We present a bi-institutional retrospective review of patients treated with multiple courses of prenatal steroids for high-risk CPAMs between 2007 and 2013. RESULTS: Nine patients met inclusion criteria. All but one either had an increased CPAM volume ratio (CVR) or number of fluid-containing compartments involved after a single course of antenatal betamethasone, prompting additional courses. Four patients stabilized, three improved and two progressed after the second course. The two cases with disease progression underwent an in utero resection. There were one in utero fetal demise and two deaths within the delivery room. Both fetuses that underwent a fetal resection died. All but one mother who delivered a viable fetus had complications of pregnancy. CONCLUSIONS: Multiple courses of antenatal betamethasone for high-risk fetal CPAMs often result in favorable short-term outcomes without the need for open fetal resection. Pregnancy complications are common and women within this cohort should be monitored closely.


Assuntos
Betametasona/administração & dosagem , Malformação Adenomatoide Cística Congênita do Pulmão/tratamento farmacológico , Doenças Fetais/tratamento farmacológico , Adulto , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/administração & dosagem , Humanos , Recém-Nascido , Injeções Intramusculares , Masculino , Gravidez , Resultado da Gravidez , Anormalidades do Sistema Respiratório/complicações , Estudos Retrospectivos
13.
Curr Mol Med ; 15(2): 138-45, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25732146

RESUMO

Methodologies for generating functional neuronal cells directly from human fibroblasts [induced neuronal (iN) cells] have been recently developed, but the research so far has only focused on technical refinements or recapitulation of known pathological phenotypes. A critical question is whether this novel technology will contribute to elucidation of novel disease mechanisms or evaluation of therapeutic strategies. Here we have addressed this question by studying Tay-Sachs disease, a representative lysosomal storage disease, and Dravet syndrome, a form of severe myoclonic epilepsy in infancy, using human iN cells with feature of immature postmitotic glutamatergic neuronal cells. In Tay-Sachs disease, we have successfully characterized canonical neuronal pathology, massive accumulation of GM2 ganglioside, and demonstrated the suitability of this novel cell culture for future drug screening. In Dravet syndrome, we have identified a novel functional phenotype that was not suggested by studies of classical mouse models and human autopsied brains. Taken together, the present study demonstrates that human iN cells are useful for translational neuroscience research to explore novel disease mechanisms and evaluate therapeutic compounds. In the future, research using human iN cells with well-characterized genomic landscape can be integrated into multidisciplinary patient-oriented research on neuropsychiatric disorders to address novel disease mechanisms and evaluate therapeutic strategies.


Assuntos
Epilepsias Mioclônicas/metabolismo , Fibroblastos/metabolismo , Gangliosídeo G(M2)/metabolismo , Neurônios/metabolismo , Doença de Tay-Sachs/metabolismo , 1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular , Epilepsias Mioclônicas/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Lentivirus/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Plasmídeos/química , Plasmídeos/metabolismo , Cultura Primária de Células , Doença de Tay-Sachs/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transdução Genética , Transgenes
14.
Ultrasound Obstet Gynecol ; 45(4): 447-51, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25157457

RESUMO

OBJECTIVES: Twin-reversed arterial perfusion (TRAP) sequence affects 1% of monochorionic twin pregnancies and is caused by abnormal vascular connections between a pump twin and an acardiac mass. The effects of abnormal vascular connections on cerebral vasculature in the pump twin are unknown. We hypothesize that abnormal cerebral vascular impedance, as assessed by the pulsatility index (PI), is present in pump twins and that fetal intervention alters cerebral impedance. METHODS: Fetal echocardiograms performed between 2010 and 2013 in pregnancies diagnosed with TRAP (n = 19), recorded at presentation, and uncomplicated monochorionic twin pregnancies (controls, n = 18; 36 fetuses) were analyzed. In all subjects, the middle cerebral artery (MCA)-PI, combined cardiac output (CCO) and cardiothoracic ratio were calculated, and the values for cases and controls were compared. RESULTS: The mean gestational age at the time of echocardiography was 20 weeks in both groups. MCA-PI was lower in TRAP cases than in controls (1.55 (95% CI, 1.47-1.64) vs 1.74 (95% CI, 1.65-1.82), respectively; P = 0.004). CCO in TRAP cases was mildly elevated for gestational age (199.7 (95% CI, 138.4-261.1) mL/min) compared with that of controls (131.4 (95% CI, 102.2-160.7) mL/min). In six TRAP cases with a second echocardiogram available, the mean MCA-PI increased after intervention, from 1.5 (95% CI, 1.3-1.7) to 1.8 (95% CI, 1.4-2.2). CONCLUSIONS: TRAP pump twins have lower cerebral vascular impedance than do controls, suggestive of a brain-sparing effect. MCA-PI appeared to increase in a small group of pump twins after intervention. These findings suggest a fetal cerebral autoregulatory response to a high cardiac output state that begins to change after fetal intervention. The long-term implications for neurodevelopmental outcome warrant further study.


Assuntos
Transfusão Feto-Fetal/fisiopatologia , Feto/irrigação sanguínea , Artéria Cerebral Média/diagnóstico por imagem , Gêmeos , Ecocardiografia , Feminino , Transfusão Feto-Fetal/diagnóstico por imagem , Feto/anormalidades , Humanos , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/fisiopatologia , Placenta/irrigação sanguínea , Placenta/diagnóstico por imagem , Gravidez , Gravidez de Gêmeos , Fluxo Pulsátil/fisiologia , Tratamento por Radiofrequência Pulsada/métodos , Taxa de Sobrevida , Ultrassonografia Pré-Natal
15.
Neuroscience ; 274: 383-92, 2014 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-24912028

RESUMO

Previous neuroimaging studies of response inhibition have examined correlations between behavioral efficiency and brain activity, but the temporal stability of the correlations has largely been ignored. The present functional magnetic resonance imaging (fMRI) study demonstrates the temporal changes of the brain activity associated with performance efficiency that led to more robust brain-behavior correlations in a later part of the experimental sessions. Participants performed a stop-signal task requiring inhibition of inappropriate responses, where more efficient behavioral performance is reflected in a shorter stop-signal reaction time (SSRT). Among across-subject negative correlations between the brain activity and the SSRT, the majority of the negative correlations were observed in the second half of experimental sessions. In the cerebellar region that showed the greatest difference in correlations between the second and the first halves, the brain activity increased in efficient performers, whereas the brain activity decreased in poor performers. These results suggest the existence of multiple brain mechanisms that increase and decrease the brain activity depending on the behavioral efficiency of the performers. More practically, these results indicate that robust brain-behavior correlations can more effectively be detected in a later part of the experimental sessions.


Assuntos
Encéfalo/fisiologia , Inibição Psicológica , Desempenho Psicomotor/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tempo de Reação/fisiologia , Adulto Jovem
16.
Blood Cancer J ; 3: e132, 2013 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-23955587

RESUMO

In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression.

17.
J Neurol Sci ; 327(1-2): 65-72, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23422026

RESUMO

Early-onset epileptic encephalopathies include various diseases such as early-infantile epileptic encephalopathy with suppression burst. We experimentally investigated the unique clinicopathological features of a 28-month-old girl with early-onset epileptic encephalopathy. Her initial symptom was intractable epilepsy with a suppression-burst pattern of electroencephalography (EEG) from 7 days of age. The suppression-burst pattern was novel, appearing during sleep, but disappearing upon waking and after becoming 2 months old. The EEG showed multifocal spikes and altered with age. Her seizures demonstrated various clinical features and continued until death. She did not show any developmental features, including no social smiling or head control. Head MRI revealed progressive atrophy of the cerebral cortex and white matter after 1 month of age. (123)IMZ-SPECT demonstrated hypo-perfusion of the cerebral cortex, but normo-perfusion of the diencephalon and cerebellum. Such imaging information indicated GABA-A receptor dysfunction of the cerebral cortex. The genetic analyses of major neonatal epilepsies showed no mutation. The neuropathology revealed atrophy and severe edema of the cerebral cortex and white matter. GAD-immunohistochemistry exhibited imbalanced distribution of GABAergic interneurons between the striatum and cerebral cortex. The results were similar to those of focal cortical dysplasia with transmantle sign and X-linked lissencephaly with ARX mutation. We performed various metabolic examinations, detailed pathological investigations and genetic analyses, but could not identify the cause. To our knowledge, her clinical and pathological courses have never been described in the literature.


Assuntos
Córtex Cerebral/patologia , Progressão da Doença , Epilepsia/diagnóstico , Neurônios GABAérgicos/patologia , Interneurônios/patologia , Índice de Gravidade de Doença , Córtex Cerebral/química , Criança , Pré-Escolar , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Evolução Fatal , Feminino , Neurônios GABAérgicos/química , Humanos , Lactente , Interneurônios/química , Fibras Nervosas Mielinizadas/química , Fibras Nervosas Mielinizadas/patologia
18.
Diabet Med ; 29(7): e138-41, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22356209

RESUMO

BACKGROUND: Insulinoma is a tumour of insulin-producing cells of the pancreas and is known to be one of the causes of hypoglycaemia. Usually, appropriate removal of the insulinoma results in normalization of blood glucose levels. However, we found novel cases of insulinoma, in which hyperglycaemia developed soon after resection of the insulinoma. CASE REPORT: We encountered two patients with repeated hypoglycaemia caused by insulinoma. Following removal of the insulinoma, unanticipated hyperglycaemia was observed in both patients. Thereafter, their blood tests revealed low levels of serum C-peptide and high titres of anti-glutamic acid decarboxylase antibody, indicating concomitant Type 1 diabetes. Indeed, histological examination of the resected specimen revealed that one patient showed insulitis in non-tumorous pancreatic tissue in which ß-cells had already disappeared. Moreover, inflammatory cells infiltrated the insulinoma, as if it were insulitis of Type 1 diabetes, suggesting the existence of anti-islet autoimmunity. CONCLUSION: These are first cases of insulinoma associated with underlying Type 1 diabetes. Physicians should be aware of the possibility that insulinoma may mask Type 1 diabetes, and measurement of anti-islet autoantibodies may be helpful to find underlying Type 1 diabetes, such as in these cases. It is pathologically interesting that the immune cell infiltration into insulinoma may be suggestive of anti-islet autoimmunity.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Hiperglicemia/diagnóstico , Insulinoma/diagnóstico , Ilhotas Pancreáticas/imunologia , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/imunologia , Insulinoma/sangue , Insulinoma/imunologia , Masculino , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/imunologia
19.
No To Hattatsu ; 41(6): 408, 2009 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-19928535

Assuntos
Medicina/normas , Ásia
20.
Neurology ; 73(15): 1214-7, 2009 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-19822871

RESUMO

OBJECTIVE: Mutations of the genes encoding subunits of potassium voltage-gated channel, KCNQ2 and KCNQ3, have been identified in patients with benign familial neonatal seizures (BFNS). This study set out to determine the frequency of microchromosomal deletions of KCNQ2 or KCNQ3 associated with BFNS. METHODS: The study subjects were patients with BFNS (n = 22). Microdeletions were sought by multiplex ligation-dependent probe amplification and then confirmed by fluorescence in situ hybridization and characterized by array-based comparative genomic hybridization. RESULTS: Heterozygous multiple exonic deletions of KCNQ2 were identified in 4 of 22 patients with BFNS. Concomitant deletions of adjacent genes, including nicotinic cholinergic receptor alpha4 (CHRNA4), were detected in 2 of the 4 cases. The clinical courses of patients with deletions of both KCNQ2 and CHRNA4 were those of typical BFNS, and none presented with the phenotype of autosomal dominant nocturnal frontal lobe epilepsy, some of which are caused by mutations of CHRNA4. CONCLUSIONS: Our findings indicate that the clinical courses of patients with deletions of both KCNQ2 and CHRNA4 are indistinguishable from those of patients with deletions of KCNQ2 only.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 20/genética , Epilepsia Neonatal Benigna/genética , Canal de Potássio KCNQ2/genética , Receptores Nicotínicos/genética , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Canal de Potássio KCNQ3/genética , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Linhagem
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