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1.
Pediatr Radiol ; 49(11): 1422-1432, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31620843

RESUMEN

Initial pediatric imaging of the liver heavily relies on ultrasonography (US) because it is free of ionizing radiation, easily portable and readily available. Although conventional US (gray-scale and color Doppler) is often an excellent screening tool, its relative low specificity compared to CT/MRI limits liver lesion characterization. The United States Food and Drug Administration's recent approval of an intravenous US contrast agent for pediatric liver lesion characterization (sulfur hexafluoride lipid-type A microspheres) and its excellent safety profile have spurred increased interest in contrast-enhanced US for definitive diagnosis of pediatric liver lesions. This review focuses on the safety of contrast-enhanced US, role of contrast-enhanced US in the evaluation of focal liver lesions, basic contrast-enhanced US technique for liver imaging, and interpretation principles. The authors review common focal liver lesions, with special attention to the role of contrast-enhanced US in the pediatric oncology population.


Asunto(s)
Medios de Contraste , Hepatopatías/diagnóstico por imagen , Ultrasonografía/métodos , Niño , Humanos
2.
J Genet ; 97(5): 1315-1325, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30555080

RESUMEN

Nodal-related protein (ndr2) is amember of the transforming growth factor type ß superfamily of factors and is required for ventral midline patterning of the embryonic central nervous system in zebrafish. In humans, mutations in the gene encoding nodal cause holoprosencephaly and heterotaxy. Mutations in the ndr2 gene in the zebrafish (Danio rerio) lead to similar phenotypes, including loss of the medial floor plate, severe deficits in ventral forebrain development and cyclopia. Alleles of the ndr2 gene have been useful in studying patterning of ventral structures of the central nervous system. Fifteen different ndr2 alleles have been reported in zebrafish, of which eight were generated using chemical mutagenesis, four were radiation-induced and the remaining alleles were obtained via random insertion, gene targeting (TALEN) or unknown methods. Therefore, most mutation sites were random and could not be predicted a priori. Using the CRISPR-Cas9 system from Streptococcus pyogenes, we targeted distinct regions in all three exons of zebrafish ndr2 and observed cyclopia in the injected (G0) embryos.We show that the use of sgRNA-Cas9 ribonucleoprotein (RNP) complexes can cause penetrant cyclopic phenotypes in injected (G0) embryos. Targeted polymerase chain reaction amplicon analysis using Sanger sequencing showed that most of the alleles had small indels resulting in frameshifts. The sequence information correlates with the loss of ndr2 activity. In this study, we validate multiple CRISPR targets using an in vitro nuclease assay and in vivo analysis using embryos. We describe one specific mutant allele resulting in the loss of conserved terminal cysteine-coding sequences. This study is another demonstration of the utility of the CRISPR-Cas9 system in generating domain-specific mutations and provides further insights into the structure-function of the ndr2 gene.


Asunto(s)
Sistemas CRISPR-Cas , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación , Ribonucleoproteínas/genética , Proteínas de Pez Cebra/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Sitios de Unión/genética , Embrión no Mamífero/embriología , Embrión no Mamífero/metabolismo , Holoprosencefalia/genética , Péptidos y Proteínas de Señalización Intracelular/química , Modelos Moleculares , Fenotipo , Dominios Proteicos , Ribonucleoproteínas/metabolismo , Pez Cebra/embriología , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/química
3.
J Nucl Med ; 59(1): 25-30, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28611244

RESUMEN

The purpose of this study was to determine the relationship of 18F-FDG uptake in the primary tumor at diagnosis, during therapy, and after therapy with a histologic response and event-free survival in pediatric and young adult patients with osteosarcoma (OS). Methods: Serial (baseline and 5 and 10 wk after start of therapy) 18F-FDG PET/CT imaging was performed in patients with newly diagnosed OS treated uniformly in a therapeutic trial at a single institution. Whole-body images were obtained approximately 1 h after injection of 18F-FDG. Logistic regression was used to study the association of tumor uptake and changes in SUVmax between 0, 5, and 10 wk for both clinical endpoints. Results: Thirty-four patients (17 males; median age, 12.2 y; age range, 6.8-19.1 y) underwent PET imaging; 25 (74%) had localized disease. Primary tumor locations included the femur (n = 17; 50%), tibia (n = 9; 26%), and humerus (n = 5; 15%). Logistic regression showed that SUVmax at 5 wk (P = 0.034) and 10 wk (P = 0.022) and percentage change from baseline at 10 wk (P = 0.021) were highly predictive of a histologic response. Using SUVmax of 4.04 at week 5, SUVmax of 3.15 at week 10, and 60% decrease from baseline at week 10 as cutoff values, we determined that the respective sensitivities were 0.93, 0.93, and 0.79 and that the respective specificities were 0.53, 0.71, and 0.76. Conclusion: SUVmax on routine images at 5 or 10 wk and percentage change in SUVmax from baseline to week 10 were metabolic predictors of a histologic response in OS. These findings may be useful in the early identification of patients who are responding poorly to therapy and may benefit from a change in treatment.


Asunto(s)
Quimioterapia Adyuvante , Fluorodesoxiglucosa F18/metabolismo , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Adolescente , Adulto , Transporte Biológico , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Factores de Tiempo
4.
J Nucl Med ; 54(11): 1902-8, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24050936

RESUMEN

UNLABELLED: The purpose of this study was to evaluate the biodistribution of (11)C-labeled methionine in non-tumor-involved organs in pediatric patients studied for malignant diseases. METHODS: Ninety-three children and young adults with known or suspected malignancies underwent (11)C-methionine PET and CT scans. Imaging began 5-15 min after injection of 740 MBq (20 mCi) per 1.7 m(2) of body surface area. Images were acquired from the top of the head through the mid thighs. Standardized uptake values were determined using regions of interest drawn on the CT image and transferred to the corresponding transverse PET slice. RESULTS: The highest concentrations of (11)C-methionine were found in the pancreas and liver. Less intense uptake was seen in other regions, such as the salivary glands, tonsils, and bone marrow. There was little uptake in the lungs, fat (including brown adipose tissue), and muscle. Uptake in bone marrow, parotid glands, and tonsils was slightly but statistically significantly higher in men than women. Testicular, bone marrow, and left ventricular uptake increased with age. There was little variability statistically between comparisons of uptake change and groupings of age, race, sex, and patients studied at the time of diagnosis versus previously treated patients. CONCLUSION: High uptake of (11)C-methionine is reliably found in the pancreas and liver, consistent with the anabolic functions of these organs. Low uptake in the brain, neck, chest, pelvis, and extremities will facilitate tumor localization in those areas. However, intense uptake in the upper abdomen may limit the diagnostic utility of (11)C-methionine in that area.


Asunto(s)
Metionina/farmacocinética , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Tomografía de Emisión de Positrones , Radiometría , Recurrencia , Factores Sexuales , Distribución Tisular , Tomografía Computarizada por Rayos X , Adulto Joven
5.
Neurosci Lett ; 524(1): 49-54, 2012 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-22820212

RESUMEN

Transient receptor potential (TRP) channels are a large family of cation channels. The 28 TRP channel subtypes in rodent are divided into 6 subfamilies: TRPC1-7, TRPV1-6, TRPM1-8, TRPP2/3/5, TRPML1-3 and TRPA1. TRP channels are involved in peripheral olfactory transduction. Several TRPC channels are expressed in unidentified neurons in the main olfactory bulb (OB), but the expression of most TRP channels in the OB has not been investigated. The present study employed RT-PCR as an initial survey of the expression of TRP channel mRNAs in the mouse OB and in 3 cell types: external tufted, mitral and granule cells. All TRP channel mRNAs except TRPV5 were detected in OB tissue. Single cell RT-PCR revealed that external tufted, mitral and granule cell populations expressed in aggregate 14 TRP channel mRNAs encompassing members of all 6 subfamilies. These different OB neuron populations expressed 7-12 channel mRNAs. Common channel expression was more similar among external tufted and mitral cells than among these cells and granule cells. These results indicate that a large number of TRP channel subtypes are expressed in OB neurons, providing the molecular bases for these channels to regulate OB neuron activity and central olfactory processing.


Asunto(s)
Bulbo Olfatorio/metabolismo , ARN Mensajero/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Bulbo Olfatorio/citología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Canales de Potencial de Receptor Transitorio/genética
6.
Biomaterials ; 31(19): 5083-90, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20378165

RESUMEN

For biomedical applications, emerging nanostructures requires stringent evaluations for their biocompatibility. Core/shell iron/carbon nanoparticles (Fe@CNPs) are nanomaterials that have potential applications in magnetic resonance imaging (MRI), magnetic hyperthermia and drug delivery. However, their interactions with biological systems are totally unknown. To evaluate their potential cellular perturbations and explore the relationships between their biocompatibility and surface chemistry, we synthesized polymer grafted Fe@CNPs with diverse chemistry modifications on surface and investigated their dynamic cellular responses, cell uptake, oxidative stress and their effects on cell apoptosis and cell cycle. The results show that biocompatibility of Fe@CNPs is both surface chemistry dependent and cell type specific. Except for the carboxyl modified Fe@CNPs, all other Fe@CNPs present low toxicity and can be used for further functionalization and in a wide range of biomedical applications.


Asunto(s)
Apoptosis/efectos de los fármacos , Materiales Biocompatibles/administración & dosificación , Carbono/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Hierro/administración & dosificación , Nanopartículas/administración & dosificación , Polímeros/química , Materiales Biocompatibles/química , Carbono/química , Línea Celular , Humanos , Hierro/química , Ensayo de Materiales , Tamaño de la Partícula , Polímeros/administración & dosificación
7.
IEEE Trans Biomed Eng ; 54(7): 1186-90, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17605349

RESUMEN

The use of peripheral nerve blocks to control pain is an increasing practice. Many techniques include the use of stimulating needles to locate the nerve of interest. Though success rates are generally high, difficulties still exist. In certain deeper nerve blocks, two needles of different geometries are used in the procedure. A smaller needle first locates a nerve bundle, and then is withdrawn in favor of a second, larger needle used for injection. The distinct geometries of these needles are shown to generate different electric field distributions, and these differences may be responsible for failures of the second needle to elicit nerve stimulation when placed in the same location as the first. A 3-D finite-difference method has been employed to numerically calculate the electric field distributions for a commercial set of stimulating needles.


Asunto(s)
Cateterismo/métodos , Estimulación Eléctrica/instrumentación , Estimulación Eléctrica/métodos , Modelos Neurológicos , Agujas , Bloqueo Nervioso/métodos , Nervios Periféricos/fisiología , Anisotropía , Simulación por Computador , Electrodos Implantados , Campos Electromagnéticos , Análisis de Elementos Finitos , Humanos , Inyecciones/métodos
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