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BACKGROUND: Craniofacial computed tomography (CT) is the diagnostic investigation of choice for craniosynostosis, but high radiation dose remains a concern. OBJECTIVE: To evaluate the image quality and diagnostic performance of an ultra-low-dose craniofacial CT protocol with deep learning reconstruction for diagnosis of craniosynostosis. MATERIALS AND METHODS: All children who underwent initial craniofacial CT for suspected craniosynostosis between September 2021 and September 2022 were included in the study. The ultra-low-dose craniofacial CT protocol using 70 kVp, model-based iterative reconstruction and deep learning reconstruction techniques was compared with a routine-dose craniofacial CT protocol. Quantitative analysis of the signal-to-noise ratio and noise was performed. The 3-dimensional (D) volume-rendered images were independently evaluated by two radiologists with regard to surface coarseness, step-off artifacts and overall image quality on a 5-point scale. Sutural patency was assessed for each of six sutures. Radiation dose was compared between the two protocols. RESULTS: Among 29 patients (15 routine-dose CT and 14 ultra-low-dose CT), 23 patients had craniosynostosis. The 3-D volume-rendered images of ultra-low-dose CT without deep learning showed decreased image quality compared to routine-dose CT. The 3-D volume-rendered images of ultra-low-dose CT with deep learning reconstruction showed higher noise level, higher surface coarseness but decreased step-off artifacts, comparable signal-to-noise ratio and overall similar image quality compared to the routine-dose CT images. Diagnostic performance for detecting craniosynostosis at the suture level showed no significant difference between ultra-low-dose CT without deep learning reconstruction, ultra-low-dose CT with deep learning reconstruction and routine-dose CT. The estimated effective radiation dose for the ultra-low-dose CT was 0.05 mSv (range, 0.03-0.06 mSv), a 95% reduction in dose over the routine-dose CT at 1.15 mSv (range, 0.54-1.74 mSv). This radiation dose is comparable to 4-view skull radiography (0.05-0.1 mSv) and lower than previously reported effective dose for craniosynostosis protocols (0.08-3.36 mSv). CONCLUSION: In this pilot study, an ultra-low-dose CT protocol using radiation doses at a level similar to skull radiographs showed preserved diagnostic performance for craniosynostosis, but decreased image quality compared to the routine-dose CT protocol. However, by combining the ultra-low-dose CT protocol with deep learning reconstruction, image quality was improved to a level comparable to the routine-dose CT protocol, without sacrificing diagnostic performance for craniosynostosis.
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Craniossinostoses , Aprendizado Profundo , Criança , Humanos , Projetos Piloto , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Craniossinostoses/diagnóstico por imagem , Crânio , AlgoritmosRESUMO
PURPOSE: Subpial hemorrhage (SPH) is a subtype of intracranial hemorrhage characterized by damage to the adjacent brain parenchyma. The aim of this study was to describe the sonographic features of SPH in neonates. METHODS: The cranial ultrasound (US) findings of neonates with SPH confirmed by brain magnetic resonance imaging (MRI) were analyzed retrospectively. Initial and follow-up US and MRI scans were reviewed by two pediatric radiologists who were blinded to both clinical history and outcomes. The US features were compared with the MRI findings. RESULTS: Sixteen patients were included (median gestational age, 38 weeks; range, 26 to 40 weeks; 69% term). SPH was detected most often in the temporal lobe (63%), and multiple SPHs were found in seven of 16 neonates, based on MRI. Acute SPH with an underlying venous infarct (UVI) was detected on US in 15 of 16 patients: small or large fan-shaped hyperechoic lesions (n=7 and 4, respectively) and gyriform hyperechoic lesions (n=4). The sonographic yin-yang sign was observed in three of the four large fan-shaped SPH cases. The accompanying findings on US were intraventricular hemorrhage (four out of six MRI-confirmed cases), and concurrent periventricular venous infarcts (five out of nine MRI-confirmed cases). In five patients, subpial cysts were observed on follow-up US or MRI (n=4 and n=4, respectively). CONCLUSION: Acute SPH with UVI can appear as a peripheral fan-shaped or gyriform hyperechoic lesion on cranial US. SPH can be detected and suspected based on the US features of SPH with the accompanying findings.
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In this study, two types of carbon nanotubes were used as ophthalmic material, and hydrogel contact lenses were polymerized by adding two types of dispersants to effectively exert the functions of carbon nanotubes. The physical properties and surfaces of the ophthalmic hydrogel lenses prepared to confirm the functionality as a dispersant were compared and analyzed to find the utility as an ophthalmic lens material. For the polymerization, single-walled carbon nanotubes (SWCNTs), single-walled carbon nanotubes carboxylic acid functionalized (SWCCNTs), 2-hydroxyethyl methacrylate (HEMA), ethylene glycol dimethacrylate (EGDMA, a crosslinking agent), and azobisisobutyronitrile (AIBN, an initiator) was used. In addition, as a dispersant, PVP (polyvinylpyrrolidone) and BYK-111 were copolymerized. As a result of this study, PVP increased the water content and decreased refractive index regardless of the type of carbon, whereas BYK-111 did not show a significant difference in basic properties. Also, PVP gradually decreased breaking strength, while BYK-111 gradually increased breaking strength. BYK-111 effectively exerted the function of carbon nanotubes, and it was confirmed whether it was dispersed through TEM. Therefore, if carbon nanotubes are used as ophthalmic materials by utilizing BYK-111, it considered to be used as functional ophthalmic lens materials.
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Lentes de Contato , Nanotubos de Carbono , Hidrogéis , Polimerização , PovidonaRESUMO
OBJECTIVES: Preoperative estimation of the insertion depth angle of cochlear implant (CI) electrodes is essential for surgical planning. The purpose of this study was to determine the cochlear size using preoperative CT and to investigate the correlation between cochlear size and insertion depth angle in morphologically normal cochlea. METHODS: Thirty-five children who underwent CI were included in this study. Cochlear duct length (CDL) and the diameter of the cochlear basal turn (distance A/B) on preoperative CT and the insertion depth angle of the CI electrode on postoperative radiographs were independently measured by two readers. Correlation between cochlear size and insertion depth angle was evaluated. Interobserver agreement was calculated using the intraclass correlation coefficient (ICC). RESULTS: The mean CDL, distance A, and distance B of 70 ears were 36.20 ± 1.57 mm, 8.67 ± 0.42 mm, and 5.73 ± 0.32 mm, respectively. The mean insertion depth angle was 431.45 ± 38.42°. Interobserver agreements of CDL, distance A/B, and insertion depth angle were fair to excellent (ICC 0.864, 0.862, 0.529, and 0.958, respectively). Distance A (r = - 0.7643) and distance B (r = - 0.7118) showed a negative correlation with insertion depth angle, respectively (p < 0.0001). However, the correlation between CDL and insertion depth angle was not statistically significant (r = - 0.2333, p > 0.05). CONCLUSIONS: The CDL and cochlear distance can be reliably obtained from preoperative CT. Distance A can be used as a predictive marker for estimating insertion depth angle during CI surgery.
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Implante Coclear , Implantes Cocleares , Criança , Cóclea/diagnóstico por imagem , Ducto Coclear/cirurgia , Humanos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To evaluate the ultrasonography (US) features of Alagille syndrome (ALGS), as compared with biliary atresia (BA) or neonatal hepatitis (NH). METHODS: Our study included 23 ALGS, 75 BA and 70 NH patients. The initial US images were retrospectively reviewed for gallbladder (GB) morphology with systemic classification, GB length and luminal area, presence of triangular-cord (TC) sign and hypertrophied hepatic-artery. The presence of anomalies associated with ALGS was evaluated. The diagnostic values of each finding and their combinations were evaluated. RESULTS: Both ALGS (57%) and BA (79%) were more frequently associated with abnormal GB shapes than NH (19%, all P<0.001). The short and small GBs were more frequently observed in ALGS and BA than in NH (all P<0.001). None in the ALGS and NH showed TC sign, while 41% in the BA did (all P<0.001). Hypertrophied hepatic-artery was noted less frequently in both ALGS (13%) and NH (14%) than in BA (83%, all P<0.001). The combination of US criteria with associated anomalies increased the positive-predictive-value for ALGS. CONCLUSION: Abnormal shaped GB with absence of the TC sign and hypertrophied hepatic-artery and presence of associated anomalies can be a differential point of ALGS.
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Síndrome de Alagille/diagnóstico por imagem , Atresia Biliar/diagnóstico por imagem , Hepatite/diagnóstico por imagem , Ultrassonografia/métodos , Anormalidades Múltiplas/diagnóstico , Diagnóstico Diferencial , Feminino , Vesícula Biliar/diagnóstico por imagem , Artéria Hepática/diagnóstico por imagem , Humanos , Hipertrofia , Lactente , Recém-Nascido , Icterícia Neonatal/diagnóstico por imagem , Icterícia Obstrutiva/diagnóstico por imagem , Masculino , Veia Porta/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: The aim of this study was to characterize the brain ultrasonographic findings of late-onset circulatory dysfunction (LCD) due to adrenal insufficiency (AI) in preterm infants. METHODS: Among the 257 preterm infants born at <33 weeks of gestation between December 2009 and February 2014 at our institution, 35 preterm infants were diagnosed with AI. Brain ultrasonographic findings were retrospectively analyzed before and after LCD in 14 preterm infants, after exclusion of the other 21 infants with AI due to the following causes: death (n=2), early AI (n=5), sepsis (n=1), and patent ductus arteriosus (n=13). RESULTS: Fourteen of 257 infants (5.4%) were diagnosed with LCD due to AI. The age at LCD was a median of 18.5 days (range, 9 to 32 days). The last ultrasonographic findings before LCD occurred showed grade 1 periventricular echogenicity (PVE) in all 14 patients and germinal matrix hemorrhage (GMH) with focal cystic change in one patient. Ultrasonographic findings after LCD demonstrated no significant change in grade 1 PVE and no new lesions in eight (57%), grade 1 PVE with newly appearing GMH in three (21%), and increased PVE in three (21%) infants. Five infants (36%) showed new development (n=4) or increased size (n=1) of GMH. Two of three infants (14%) with increased PVE developed cystic periventricular leukomalacia (PVL) and rapid progression to macrocystic encephalomalacia. CONCLUSION: LCD due to AI may be associated with the late development of GMH, increased PVE after LCD, and cystic PVL with rapid progression to macrocystic encephalomalacia.
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OBJECTIVES: To compare image quality and radiation dose between high-pitch mode (HPM) and low-pitch mode (LPM) CT in young children. MATERIALS AND METHODS: Forty-seven children (mean age 35.6 months; range, 0-126 months) underwent 49 CT examinations in HPM or LPM and were divided into high or low respiratory rate (RR) groups. A qualitative image quality was compared between the two modes. The volume CT dose index (CTDIvol) and dose-length product (DLP) were evaluated from the dose reports, and effective doses were assessed using a paediatric phantom. RESULTS: Image quality was generally better for HPM than LPM (diagnostic acceptance score, 4.00 vs. 3.46, P = 0.004); the difference was more prominent in the high RR group (4.00 vs. 3.22, P = 0.001). However, there was no significant difference in the low RR group. The mean DLP value was higher in HPM than LPM (29.48 mGy · cm vs. 23.46 mGy · cm, P = 0.022), while CTDIvol was not significantly different. The total effective radiation dose was 26 % higher in HPM than LPM (1.82 mSv vs. 1.44 mSv). CONCLUSIONS: LPM can be considered for paediatric lung evaluation in young children with low RRs to reduce radiation dose while maintaining favourable image quality. KEY POINTS: ⢠Radiation exposure is higher on high-pitch "Flash spiral mode" than on low-pitch "X-CARE mode". ⢠"Flash spiral mode" generally showed better image quality than "X-CARE mode". ⢠Difference in image quality was more prominent in the high RR group. ⢠There was no difference in image quality in the low RR group. ⢠"X-CARE mode" should be considered in a limited population with low RRs.
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Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Doses de Radiação , Taxa Respiratória/fisiologia , Tomografia Computadorizada Espiral/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Imagens de FantasmasRESUMO
INTRODUCTION: This study aimed to assess the therapeutic results of ultrasound (US)-guided water-soluble contrast enema in very low birth weight (VLBW) preterm infants (<1,500 g) with meconium obstruction and to study factors that affect therapeutic results. METHODS: This study included a total of 33 consecutive VLBW infants with clinically diagnosed meconium obstruction underwent US-guided water-soluble contrast enema, from April 2007 to March 2014. Patients were classified into two groups based on to procedure outcome: the success group (evacuation of the meconium plug resolution followed by improved bowel distention within 2 days of the procedure, without additional interventions), and the failure group (the contrast enema failed to relieve the obstruction, or other procedure-related complications occurred). Patient- and mother-related clinical factors and procedure-related factors were compared between both groups. RESULTS: Overall success rate was 54.5%, with 18 successful (M:F=10:8), and 15 failure (M:F=7:8) cases. When compared with the failure group, the success group patients showed statistically significant older gestational age (29(+1) vs. 27 weeks; p=0.028), larger birth weight (1023.1g vs. 790.3g; p=0.048), and higher body weight on the day of the procedure (1036.2g vs. 801.6g, p=0.049). However, no statistically significant differences were seen between other patient and maternal factors. Among the procedure-related factors, retrial of contrast injection during the procedure was associated with significantly higher success than the single trial (p=0.027). The presence of refluxed contrast into the distal ileum was the statistically significant predictor for success of the procedure (p=0.038). There were three cases of bowel perforation (9.1% per person). CONCLUSION: US-guided water-soluble contrast enema in VLBW infants with meconium obstruction showed a 54.5% success rate and a 9.1% perforation rate per person. Among the procedure-related factors, retrial of contrast injection during the procedure and the presence of refluxed contrast into the distal ileum were related to the success of the procedure.
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Catárticos/uso terapêutico , Meios de Contraste/uso terapêutico , Enema/métodos , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Obstrução Intestinal/terapia , Mecônio , Ultrassonografia de Intervenção/métodos , Acetilcisteína/uso terapêutico , Peso ao Nascer , Diatrizoato de Meglumina/uso terapêutico , Expectorantes/uso terapêutico , Feminino , Idade Gestacional , Humanos , Doenças do Íleo/diagnóstico por imagem , Recém-Nascido , Obstrução Intestinal/diagnóstico por imagem , Perfuração Intestinal/etiologia , Ácido Iotalâmico/análogos & derivados , Ácido Iotalâmico/uso terapêutico , Masculino , Mecônio/diagnóstico por imagem , Radiografia , Retratamento , Cloreto de Sódio/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
All-trans retinoic acid (ATRA) inhibits matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fibroblasts, skin fibroblasts, bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells (HDPCs). The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and -9 in HDPCs. The productions and messenger RNA (mRNA) expressions of MMP-2 and -9 were accessed by gelatin zymography and real-time polymerase chain reaction (PCR), respectively. ATRA was found to decrease MMP-2 level in a dose-dependent manner. Significant reduction in MMP-2 mRNA expression was also observed in HDPCs treated with 25 µmolâ L(-1) ATRA. However, HDPCs treated with ATRA had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. Taken together, ATRA had an inhibitory effect on MMP-2 expression in HDPCs, which suggests that ATRA could be a candidate as a medicament which could control the inflammation of pulp tissue in vital pulp therapy and regenerative endodontics.
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Polpa Dentária/enzimologia , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Tretinoína/farmacologia , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , RNA Mensageiro/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Gênica/efeitos dos fármacos , Tretinoína/administração & dosagemRESUMO
OBJECTIVE: To develop an high resolution computed tomography (HRCT) scoring system for the assessment of bronchopulmonary dysplasia (BPD) and determine its usefulness as compared with the chest radiographic score. MATERIALS AND METHODS: Forty-two very low-birth-weight preterm infants with BPD (25 male, 17 female) were prospectively evaluated with HRCT performed at the mean age of 39.1-week postmenstrual age. Clinical severity of BPD was categorized as mild, moderate or severe. The HRCT score (0-36) of each patient was the sum of the number of bronchopulmonary segments with 1) hyperaeration and 2) parenchymal lesions (linear lesions, segmental atelectasis, consolidation and architectural distortion), respectively. We compared the HRCT scores with the chest radiographic scores (the Toce system) in terms of correlation with clinical severity. RESULTS: The HRCT score had good interobserver (r = 0.969, p < 0.001) and intraobserver (r = 0.986, p < 0.001) reproducibility. The HRCT score showed better correlation (r = 0.646, p < 0.001) with the clinical severity of BPD than the chest radiographic score (r = 0.410, p = 0.007). The hyperaeration score showed better correlation (r = 0.738, p < 0.001) with the clinical severity of BPD than the parenchymal score (r = 0.523, p < 0.001). CONCLUSION: We have developed a new HRCT scoring system for BPD based on the quantitative evaluation of pulmonary abnormalities of BPD consisting of the hyperaeration score and the parenchymal score. The HRCT score shows better correlation with the clinical severity of BPD than the radiographic score.
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Displasia Broncopulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: The purpose of this study was to evaluate retrospectively the CT and sonographic features in nine children with pathologically proven inflammatory myofibroblastic tumors of the abdomen. CONCLUSION: Although inflammatory myofibroblastic tumors occur in various sites and the imaging characteristics are variable, tumors showed different imaging patterns that were dependent on the site at which the tumor had originated.
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Abdome/patologia , Granuloma de Células Plasmáticas/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Meios de Contraste , Diagnóstico Diferencial , Feminino , Granuloma de Células Plasmáticas/patologia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
OBJECTIVE: The purpose of our study was to determine whether CT provides additional information for children with a suspected residual foreign body in the airway after bronchoscopy. MATERIALS AND METHODS: We reviewed the CT findings and medical records of nine patients (five girls and four boys; mean age, 17.9 months) who underwent CT between March 1999 and February 2007 for the evaluation of a clinically suspected residual foreign body in the airway after bronchoscopy. We evaluated the location and pattern of bronchial obstruction and associated parenchymal abnormalities on CT. CT findings were compared with a second bronchoscopy in five patients. The remaining four patients were followed clinically. Association between CT findings and results on second bronchoscopy was evaluated with Fisher's exact test. RESULTS: CT after bronchoscopy (n = 9) showed bronchial obstruction in eight patients with focal complete (n = 3), diffuse (n = 3), or combined type (n = 2) bronchial obstruction. These obstructions were not seen at chest radiography. CT revealed unilateral or lobar emphysema (n = 6), atelectasis (n = 6), and consolidation (n = 1). The remaining one patient showed no abnormality on CT. A second bronchoscopy (n = 5) confirmed the focal complete bronchial obstruction at CT (n = 3) as retained foreign body fragments (n = 2) or mucus plug (n = 1) and the combined type at CT (n = 2) as retained foreign body fragments, granulation tissue, and edema of the bronchus (n = 1) or retained foreign body fragments, granulation tissue, and mucus plug (n = 1). There was a significant association between CT findings of type of bronchial obstruction and intrabronchial obstructive lesion on the second bronchoscopy (p = 0.036). CONCLUSION: CT after bronchoscopy can provide additional information regarding the presence and pattern of bronchial obstruction in children with a suspected residual foreign body.
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Brônquios/patologia , Broncografia/métodos , Broncoscopia , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/patologia , Tomografia Computadorizada por Raios X/métodos , Traqueia/diagnóstico por imagem , Traqueia/patologia , Pré-Escolar , Reações Falso-Negativas , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Central skull base tumours are rare in children. OBJECTIVE: To characterize the imaging features of central skull base lymphoma in children to aid its diagnosis. MATERIALS AND METHODS: The authors reviewed the CT findings (available in three patients) and MR findings (available in four patients) in four patients (three boys, one girl; age 2-12 years) with pathologically proven lymphoma (two with Burkitt lymphoma, two with B-cell lymphoma) involving the central skull base. Tumour location and extent, MRI signal intensities, noncontrast CT attenuation, patterns of enhancement, and changes in adjacent structures were evaluated. RESULTS: All four tumours involved the sphenoid bone. In three patients, the tumour extended to the ethmoid sinus and both cavernous sinuses. All lesions were isointense solid masses on T2-weighted images and showed avid enhancement, except for one lesion with a focal necrosis. All tumours were associated with adjacent dural thickening. Non-contrast CT showed highly attenuating masses and permeative bone destruction in the central skull base. CONCLUSION: Lymphoma involving the central skull base in children is visualized as an isointense mass on T2-weighted MRI with marked contrast enhancement and adjacent dural thickening, and as a highly attenuating mass on noncontrast CT with permeative or erosive bone destruction patterns.
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Linfoma/diagnóstico , Imageamento por Ressonância Magnética/métodos , Neoplasias da Base do Crânio/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
4-1BB, one of co-stimulatory molecules, is a member of TNF receptor superfamily and expressed on T cells upon TCR ligation. We have shown that 4-1BB is a co-stimulatory molecule enhancing cell cycle progression and inhibiting activation-induced cell death of CD8+ T cells by enhancing TCR signaling pathways. Here, we first report that the cross-linking of 4-1BB increased the expression of IL-13 mRNA and protein, and its secretion apparently via calcineurin, a Ca2+/calmodulin-dependent phosphatase. Ligation of 4-1BB with p815-m-4-1BBL evoked intracellular Ca2+ level in CD8+ T cells. CD8+ T cells express IL-13 receptor alpha1 mRNA. Incubation with anti-IL-13 blocking mAb reduced proliferation of CD8+ T cells enhanced by 4-1BB, and the treatment of CD3/4-1BB-ligated CD8+ T cells with recombinant IL-13 enhances cell proliferation, indicating that 4-1BB-induced IL-13 expression is partially responsible for the CD8+ T cell expansion in an autocrine or paracrine manner.
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Ligante 4-1BB/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Reagentes de Ligações Cruzadas/metabolismo , Interleucina-13/metabolismo , Regulação para Cima , Animais , Cálcio/metabolismo , Citosol/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Cross-linking of 4-1BB, a member of the TNFR family, increased tyrosine phosphorylation of TCR-signaling molecules such as CD3epsilon, CD3zeta, Lck, the linker for activation of T cells, and SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76). In addition, incubation of activated CD8+ T cells with p815 cells expressing 4-1BBL led to redistribution of the lipid raft domains and Lck, protein kinase C-theta;, SLP-76, and phospholipase C-gamma1 (PLC-gamma1) on the T cell membranes to the areas of contact with the p815 cells and recruitment of 4-1BB, TNFR-associated factor 2, and phospho-tyrosine proteins to the raft domains. 4-1BB ligation also caused translocation of TNFR-associated factor 2, protein kinase C-theta;, PLC-gamma1, and SLP-76 to detergent-insoluble compartments in the CD8+ T cells, and cross-linking of 4-1BB increased intracellular Ca2+ levels apparently by activating PLC-gamma1. The redistribution of lipid rafts and Lck, as well as translocation of PLC-gamma1, and degradation of IkappaB-alpha in response to 4-1BB were inhibited by disrupting the formation of lipid rafts with methyl-beta-cyclodextrin. These findings demonstrate that 4-1BB is a T cell costimulatory receptor that activates TCR-signaling pathways in CD8+ T cells.