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Objective: To investigate the risk factors and prognostic impact of massive introperative blood loss in posterior spinal fusion (PSF) surgery for adolescent idiopathic scoliosis (AIS). Methods: Clinical data were collected of 1 896 AIS patients who underwent PSF surgery under general anesthesia in Drum Tower Hospital Affiliated to Nanjing University Medical School from November 2010 to October 2019 and retrospectively analyzed. According to the volume of intraoperative blood loss, the patients were divided into the massive introperative blood loss group [estimated blood loss (EBL)/estimated blood volume (EBV)≥30%] and the non-massive introperative blood loss group (EBL/EBV<30%). The perioperative parameters between the two groups were compared, single factor analysis and multivariate logistic regression analysis was performed to identify independent risk factors related to massive introperative blood loss in PSF surgery. Results: A total of 1 896 AIS patients who underwent PSF surgery were included in the study. There were 298 males and 1 598 females, with an age of (14.5±1.7) years. Among them, 633 (33%) experienced massive intraoperative blood loss. The factors significantly related to the massive blood loss during PSF surgery in this study are: sex, body mass index(BMI), preoperative blood platelet count (PLT), prothrombin time, international normalized ratio(INR), preoperative Cobb angle, duration of operation, the number of fused levels, the number of screws, thoracoplasty, intraoperative use of tranexamic acid and dexmedetomidine; The independent factors included duration of operation longer than 4 hours(OR=4.311,P<0.001), the number of fused levels to be more than 10(OR=4.044,P<0.001), thoracoplasty (OR=2.174,P=0.019), BMI lower than 18.1 kg/m2(OR=2.094,P<0.001), preoperative PLT less than 186.5×109/L(OR=1.480,P=0.009), preoperative INR larger than 1 (OR=1.531,P=0.003) and preoperative Cobb angle larger than 53°(OR=1.306,P=0.036) ;Intraoperative use of tranexamic acid (OR=0.770, P=0.047) and dexmedetomidine (OR=0.653, P=0.008) are protective factors for massive intraoperative blood loss. In addition, in the massive intraoperative blood loss group, length of postoperative hospital stay (P<0.001), volume of postoperative incision drainage (P<0.001), postoperative allogeneic blood transfusion rate (22.7% vs 14.3%, P<0.001), incidence of postoperative hypoalbuminemia (90.3% vs 80.7%, P<0.001) and the number of rescue opioid analgesic requirements after surgery (P=0.006) were significantly higher than those in the non-massive introperative blood loss group. Conclusions: Longer operation duration, higher number of fusion levels, lower BMI, lower preoperative PLT, higher INR, larger preoperative Cobb angle and intraoperative thoraplasty are independent risk factors for massive intraoperative blood loss in AIS patients undergoing PSF surgery. Intraoperative use of tranexamic acid and dexmedetomidine can reduce the risk of massive blood loss in PSF surgery. Massive intraoperative blood loss significantly affects the patient's prognosis.
Assuntos
Cifose , Escoliose , Fusão Vertebral , Adolescente , Perda Sanguínea Cirúrgica , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Escoliose/cirurgia , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) is the sixth common malignancies worldwide and the leading cause of death in Asian and African countries. Aberrant accumulation of lncRNAs is one of major causes of tumorigenesis in HCC. Small nucleolar RNA host gene 16 (SNHG16) is identiï¬ed as an oncogene in multiple types of tumor. However, the role of SNHG16 in HCC is poor understood. Here, we showed that SNG16 was up-regulated and associated with poor prognosis in HCC. Then, we demonstrated that SNHG16 interacted with miR-302a-3p and depressed its expression. Moreover, our result indicated that SNHG16/miR-302a-3p axis regulated the expression of FGF19 in liver cancer cells. Finally, we investigated the biological function of SNHG16 in HCC and showed that SNHG16 promoted liver cancer cells proliferation via the SNHG16/miR-302a-3p/FGF19 axis. Collectively, these data suggest that SNHG16 might be a predictive biomarker and a potential therapeutic target of liver cancer.
Assuntos
Carcinoma Hepatocelular , Fatores de Crescimento de Fibroblastos , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismoRESUMO
Whether indoor painting aggravates preexisting allergic diseases remains unclear. We aimed to evaluate the impact of new classroom painting on aggravation of asthma, allergic rhinitis (AR), and atopic dermatitis (AD) in children. Studied school was previously painted with conventional water-based paint 20 years ago and had natural ventilation system. We identified a total of 172 children aged 10-12 years with allergic diseases in 17 classrooms, which were allocated to newly painted rooms with low-volatile organic compounds (VOC), water-based paint, or existing rooms. After painting, there was no intervention or internal airflow to influence indoor air environment in both classrooms. We prospectively assessed the symptom severity and serious events of allergic diseases between both classrooms at baseline and after one and eight weeks after painting. At one and eight weeks, there were no significant changes in the Childhood Asthma Control Test scores, the fractional nitric oxide levels, lung function in asthmatic children in either classroom. There were also no significant changes in the severity score of AR or AD, or serious events in all allergic diseases. These findings suggest classroom painting with this new paint at the levels encountered in this study might not be a major aggravating factor for school-aged children with allergic diseases.
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Poluição do Ar em Ambientes Fechados/efeitos adversos , Hipersensibilidade/etiologia , Pintura/toxicidade , Exacerbação dos Sintomas , Compostos Orgânicos Voláteis/toxicidade , Poluição do Ar em Ambientes Fechados/análise , Asma/induzido quimicamente , Criança , Dermatite Atópica/induzido quimicamente , Feminino , Humanos , Masculino , Pintura/análise , Estudos Prospectivos , Rinite Alérgica/induzido quimicamente , Compostos Orgânicos Voláteis/análiseRESUMO
Familial hemophagocytic lymphohistiocytosis (F-HLH or FHL) is a potentially fatal immune dysregulation syndrome with a heterogeneous genetic background. Most recently, STXBP2 has been identified as the causative gene of type 5 FHL (FHL5) with a worldwide distribution. In this study, we investigated the prevalence of FHL5 in Korea. About 50 Korean pediatric patients with HLH who lacked pathogenic mutations in PRF1, UNC13D, or in STX11 from the previous series of 72 patients with HLH were analyzed for STXBP2 mutations by conventional sequencing analyses. As a result, we found one patient with two novel mutations of STXBP2: c.184A>G and c.577A>C. c.184A>G (p.Asn62Asp) was located within a highly conserved region of the STXBP2 protein and predicted to be deleterious. c.577A>C in exon 7 resulted in incomplete splicing mutation with exon 7 skipping concurrent with exon 7-retained transcript with p.Lys193Gln substitution. The frequency of FHL5 was ~1% (1/72) in Korean pediatric patients with HLH. This is the first study on FHL5 in Korea, and the data from a nationwide patient cohort provide another piece of genetic profiles of FHL.
Assuntos
Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/genética , Proteínas Munc18/genética , Mutação/genética , Adolescente , Sequência de Aminoácidos , Sequência de Bases , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Proteínas Munc18/química , Prevalência , Estrutura Terciária de Proteína , RNA/genética , República da CoreiaRESUMO
OBJECTIVE: The purpose of this study was to compare the oral microbiome of siblings with and without dental caries using next-generation sequencing. MATERIALS AND METHODS: To investigate the oral microbiome composition, 14 young siblings, seven with caries and seven without, were enrolled from seven sibling-pair families. Supragingival plaque samples were collected from the cervicobuccal area of posterior teeth. All samples were analyzed by pyrosequencing, based on the 16S rRNA gene hypervariable regions, V1-V4. RESULTS: The organisms identified belonged to 65 genera. Fifty-two genera were identified in the subjects with caries and 58 in those without; 45 genera were shared by both groups. In the Shannon index, the caries group showed lower bacterial diversity than the caries-free group and the difference was significant (Wilcoxon signed-rank test, P < 0.05). Additionally, similarities between siblings were evident in analyses based on weighted UniFrac distances (P < 0.05). CONCLUSIONS: In this study, the diversity of the microbiome was reduced in subjects with dental caries, while similarity between siblings seemed to be retained.
Assuntos
Boca/microbiologia , Cárie Dentária/microbiologia , Humanos , Projetos Piloto , IrmãosRESUMO
The new allele, HLA-C*03:280 differs from C*03:04:01 by one nucleotide substitution at codon 35 (CGGâCAG).
Assuntos
Genes MHC da Classe II , Antígenos HLA-C/isolamento & purificação , Adulto , Alelos , Substituição de Aminoácidos , Povo Asiático/genética , Sequência de Bases , Éxons/genética , Antígenos HLA-C/genética , Teste de Histocompatibilidade , Humanos , Masculino , Dados de Sequência Molecular , República da Coreia , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
Absolute cross sections for isotopically identified products formed in multinucleon transfer in the (136)Xe+(198)Pt system at â¼8 MeV/nucleon are reported. The isotopic distributions obtained using a large acceptance spectrometer demonstrated the production of the "hard-to-reach" neutron-rich isotopes for Z<78 around the N=126 shell closure far from stability. The main contribution to the formation of these exotic nuclei is shown to arise in collisions with a small kinetic energy dissipation. The present experimental finding corroborates for the first time recent predictions that multinucleon transfer reactions would be the optimum method to populate and characterize neutron-rich isotopes around N=126 which are crucial for understanding both astrophysically relevant processes and the evolution of "magic" numbers far from stability.
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BACKGROUND: Periostin is a matricellular protein, and its synthesis in airway epithelial cells and lung fibroblasts is induced by interleukin (IL)-4 and IL-13. The significance of periostin as a biomarker of TH 2-induced airway inflammation, and (importantly) as a measure of the response to TH 2-targeted therapy, has recently been emphasized. We explored the relationship between periostin and airway hyperresponsiveness (AHR) in asthmatic children. METHODS: The study included 83 children aged 6-15 years in an asthmatic group (n = 54) and healthy controls (n = 29). We measured the periostin levels in serum and performed methacholine and mannitol provocation challenges. The responses to mannitol were expressed as the provocative dose causing a 15% fall in the FEV1 (the PD15 dose). RESULTS: Of the 54 subjects with asthma, all had positive methacholine bronchial provocation test (BPT) results and 38 had positive mannitol BPT results. Children with asthma had significantly higher periostin levels than controls [76.0 (65.0-91.8) vs 71.0 (57.5-80.0) ng/mL; P = 0.017]. Periostin levels were significantly correlated with both the methacholine PC20 and mannitol PD15 values. CONCLUSION: Serum levels of periostin, a new biomarker induced by IL-13, were higher in asthmatic children, and were associated with AHR to methacholine and mannitol.
Assuntos
Asma/sangue , Testes de Provocação Brônquica , Broncoconstritores , Moléculas de Adesão Celular/sangue , Manitol , Cloreto de Metacolina , Hipersensibilidade Respiratória/sangue , Adolescente , Asma/fisiopatologia , Estudos de Casos e Controles , Criança , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/fisiopatologiaRESUMO
OBJECTIVE: To investigate whether serum leucine-rich α2-glycoprotein (LRG) levels are elevated in patients with adult-onset Still's disease (AOSD) and determine their correlation with disease activity parameters. METHOD: We enrolled 39 patients with AOSD, 47 patients with rheumatoid arthritis (RA), and 39 controls. Forty-five serum samples from the patients with AOSD were assayed for LRG using an enzyme-linked immunosorbent assay (ELISA). Comprehensive AOSD activity was determined by a modified Pouchot score. RESULTS: Serum LRG levels were significantly elevated in patients with AOSD (128.8±40.8 ng/mL) compared to those in patients with RA and in controls (33.9±15.2 ng/mL, p<0.001 and 22.4±6.1 ng/mL, p<0.001, respectively). Patients with active AOSD had significantly higher LRG levels than those with inactive disease (141.4±31.3 ng/mL vs. 79.8±37.1 ng/mL, p=0.002). Serum LRG levels were positively correlated with C-reactive protein (CRP; γ=0.387, p=0.015), lactate dehydrogenase (LDH; γ=0.370, p=0.026), ferritin (γ=0.687, p<0.001) levels, and the modified Pouchot score (γ=0.756, p<0.001). Serum LRG levels decreased significantly after treatment in all six patients with active AOSD who had follow-up evaluations (p=0.007). The best cut-off value for LRG to distinguish AOSD from RA was 67.9 ng/mL, with a sensitivity of 92.3% and a specificity of 97.9%. CONCLUSIONS: Serum LRG levels were increased in patients with AOSD and correlated well with disease activity measures. LRG may be a useful biomarker for distinguishing AOSD from RA and for monitoring the disease activity of AOSD.
Assuntos
Progressão da Doença , Glicoproteínas/sangue , Índice de Gravidade de Doença , Doença de Still de Início Tardio/diagnóstico , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Ferritinas/sangue , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Doença de Still de Início Tardio/sangueRESUMO
OBJECTIVES: The aim of this study was to determine the clinical efficacy of the newly developed OrthoMTA and RetroMTA, compared to conventionally used ProRoot MTA, for pulpotomy in primary teeth. MATERIAL AND METHODS: In this randomized clinical trial, 151 molars from 102 children, who met the inclusion criteria and were 3-10 years old, were enrolled. Ultimately, 143 teeth were divided in a randomized, single-blind manner into three groups according to the planned treatment: RetroMTA (n = 49 teeth), OrthoMTA (n = 47 teeth) or ProRoot MTA (n = 47 teeth). Clinical and radiographic follow-up examinations were conducted at 3, 6 and 12 months postoperatively. RESULTS: By the end of the study period, 109 teeth were evaluated at 12 months. The radiographic success rates in these three groups were 100%, 94.7% and 94.7%, respectively; the corresponding clinical success rates were 100%, 97.4% and 100%. The Kaplan-Meier survival function curves relative to clinical and radiographic cumulative survival rates did not differ significantly between the three groups. CONCLUSIONS: The success rates of RetroMTA, OrthoMTA and ProRoot MTA are indistinguishable, indicating that pulpotomy can be carried out successfully in primary molars with the newly developed materials.
Assuntos
Compostos de Alumínio/uso terapêutico , Compostos de Cálcio/uso terapêutico , Óxidos/uso terapêutico , Agentes de Capeamento da Polpa Dentária e Pulpectomia/uso terapêutico , Pulpotomia , Silicatos/uso terapêutico , Dente Decíduo , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Masculino , Método Simples-Cego , Dente Decíduo/diagnóstico por imagem , Resultado do TratamentoRESUMO
OBJECTIVES: Rheumatoid factor (RF) can be seen in hepatitis B virus (HBV) infection. We investigated RF positive rates according to various HBV infectious statuses and vaccination, and the relationship between RF titers and serum HBV DNA levels. METHODS: We examined 13,670 individuals who visited the Severance Hospital in Seoul, Korea, for a routine health check-up, and obtained serum samples from all individuals. RESULTS: RF was positive in 3.5% of all subjects, and HBsAg was positive in 4.3%. HBsAg was positive in 21.7% of all RF positive subjects. RF was positive in 17.5% of the HBsAg positive group, while it was positive in 2.9% of the HBsAg negative group (p<0.001). The RF positive rate was increased in positive HBsAg, female sex, and older age. The RF positive rate was lower in those who had anti-HBs after HBV vaccination than in HBsAg positive subjects (2.7% vs. 17.5%, p<0.001). Among the RF positive patients, the RF titer in HBsAg positive patients were higher than that in HBsAg negative patients (159.7±217.1IU/mL vs. 83.0±179.2 IU/mL, p=0.001). The load of HBV DNA may be closely correlated with RF titer in patients with chronic hepatitis B (r=0.508, p=0.005). CONCLUSIONS: Persistent HBV infection is an important cause for the positive RF in HBV endemic areas. Hepatitis B viral load is associated with RF titer. HBV vaccination may reduce the risk of RF formation.
Assuntos
DNA Viral/sangue , Vírus da Hepatite B , Hepatite B , Fator Reumatoide , Adulto , Fatores Etários , Feminino , Hepatite B/epidemiologia , Hepatite B/imunologia , Hepatite B/fisiopatologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , República da Coreia/epidemiologia , Fator Reumatoide/análise , Fator Reumatoide/sangue , Fatores Sexuais , Estatística como Assunto , Carga ViralRESUMO
OBJECTIVE: The purposes of this study were to isolate and characterize stem cells from inflamed pulp tissue of human functional deciduous teeth (iSHFD) and to evaluate the influence of fibroblastic growth factor-2 (FGF-2) on the regenerative potential. MATERIALS AND METHODS: We successfully isolated mesenchymal stem cells (MSCs) from the inflamed dental pulp tissue of human deciduous teeth and demonstrated that their regenerative potential could be enhanced by the application of FGF-2 (20 ng ml(-1)) during ex vivo expansion. Isolated stem cells expanded in FGF-2 were characterized using a colony-forming assay, proliferation, migration, in vitro differentiation, in vivo ectopic transplantation assay, and gene expression profiling. RESULTS: MSCs isolated from the inflamed pulp tissue of functional deciduous teeth potentially possess the qualities of those from human exfoliated deciduous teeth. FGF-2 applied to iSHFD during expansion enhanced the colony-forming efficiency of these cells, increased their proliferation and migration potential, and reduced their differentiation potential in vitro. However, the ectopic transplantation of iSHFD/FGF-2 in vivo increased the formation of dentin-like material. CONCLUSION: FGF-2 expansion of stem cells from inflamed pulp tissues of human deciduous teeth can be a good source of stem cells for future clinical applications and a novel way of using discarded inflamed tissues.
Assuntos
Polpa Dentária/citologia , Fator 2 de Crescimento de Fibroblastos/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Pulpite/patologia , Diferenciação Celular , Células Cultivadas , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Dente DecíduoRESUMO
Klinefelter syndrome (KS) is a common sex chromosome disorder and is characterized by small, firm testes with hyalinization of the seminiferous tubules, elevated gonadotropins and azoospermia. Among karyotypic variants of KS, mosaicism 47,XXY/46,XX is extremely rare. We report here a case of an 18-year-old boy with a mosaic 47,XXY/46,XX karyotype of peripheral blood diagnosed as KS. The boy presented with anterior mediastinal mass which was confirmed as combined carvenous lymphangioma and mixed germ cell tumor by histologic examination of resected tissue. He had the male phenotype, however, azoospermia was incidentally detected on sperm banking analysis, performed prior to chemotherapy for mixed germ cell tumor. He had small and firm testes, mild gynecomastia, collectively tanner stage IV, mild hypergonadotropic hypogonadism and no evidence of true hermaphroditism. This report presents a rare case of mosaicism 47,XXY/46,XX karyotype in a phenotypic male with KS and mediastinal germ cell tumors. Based on what we experienced and review of the literature, cytogenetic analysis is recommended when physicians are confronted with a young patient with mediastinal germ cell tumor.
Assuntos
Síndrome de Klinefelter/genética , Neoplasias do Mediastino/genética , Mosaicismo , Neoplasias Embrionárias de Células Germinativas/genética , Adolescente , Azoospermia/genética , Azoospermia/patologia , Humanos , Cariótipo , Síndrome de Klinefelter/patologia , Masculino , Neoplasias do Mediastino/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , FenótipoRESUMO
The new allele, HLA-C*03:04:36, differs from C*03:04:01:01 by one nucleotide substitution at codon 207 (GGCâGGT).
Assuntos
Alelos , Antígenos HLA-C/genética , Teste de Histocompatibilidade , Análise de Sequência de DNA , Sequência de Bases , Humanos , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
The clinical impact of antimicrobial resistance on the outcome of pneumococcal bacteraemia has remained unclear. This study aimed to evaluate risk factors for mortality and determine the impact of antimicrobial resistance on clinical outcomes. A total of 150 adult patients with pneumococcal bacteraemia were identified over a period of 11 years at Seoul National University Hospital. Of the 150 patients, 122 (81.3%) had penicillin-susceptible (Pen-S) strains and 28 (18.7%) penicillin-non-susceptible (Pen-NS) strains; 43 (28.7%) had erythromycin-susceptible (EM-S) strains and 107 (71.3%) erythromycin-non-susceptible (EM-NS) strains. On multivariate analysis, elevated APACHE II score [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.14-1.34, P<0.001) and presence of solid organ tumour (OR 2.99, 95% CI 1.15-7.80, P=0.025) were independent risk factors for mortality. Neither erythromycin resistance nor penicillin resistance had a significant effect on clinical outcomes. However, for the 76 patients with pneumococcal pneumonia, the time required for defervescence was significantly longer in the EM-NS group than in the EM-S group (5.45 ± 4.39 vs. 2.93 ± 2.56, P=0.03 by log rank test). In conclusion, antimicrobial resistance does not have an effect on mortality in adult patients with pneumococcal bacteraemia.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/mortalidade , Farmacorresistência Bacteriana , Infecções Pneumocócicas/mortalidade , Streptococcus pneumoniae/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bacteriemia/microbiologia , Estudos de Coortes , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Streptococcus pneumoniae/isolamento & purificação , Resultado do Tratamento , Adulto JovemRESUMO
The radioactive aerosol generated by the Nuclear Power Plant (NPP) decommissioning process can be inhaled by workers and deposited inside the human body, resulting in internal exposure. Because internal exposure, unlike external exposure, is difficult to measure directly, it is all the more necessary to assess the dose workers receive as a result of internal exposure. Precise assessment of the internal exposure necessitates actual measurements in the work environment such as the workers' respiration rate, kind of nuclide and amount of captured nuclide. However, in the event of difficulties in securing these measurements, the internal exposure dose can be estimated based upon the recommended values by the ICRP (International Commission on Radiological Protection) such as the intake fraction and particle size. In this study, 5 µm was selected as the particle size as recommended by the ICRP, and both heavy and light respiratory rates were used in the calculation. With respect to the nuclides contained in the radioactive aerosol and their concentrations, the data captured for the aerosol in the melting facility on the Kozloduy NPP premises in Bulgaria were applied to estimate workers' internal exposure. As a result, each worker was found not to have received more than 20 mSv/yr, which is the maximum annual permissible dose for workers.
Assuntos
Exposição Ocupacional , Proteção Radiológica , Aerossóis , Bulgária , Humanos , Centrais Nucleares , Exposição Ocupacional/análise , Doses de RadiaçãoRESUMO
Vav is a hematopoietic cell-specific guanine nucleotide exchange factor (GEF) whose activation is mediated by receptor engagement. The relationship of Vav localization to its function is presently unclear. We found that Vav redistributes to the plasma membrane in response to Fcin receptor I (FcinRI) engagement. The redistribution of Vav was mediated by its Src homology 2 (SH2) domain and required Syk activity. The FcinRI and Vav were found to colocalize and were recruited to glycosphingolipid-enriched microdomains (GEMs). The scaffold protein, linker for activation of T cells (LAT), and Rac1 (a target of Vav activity) were constitutively present in GEMs. Expression of an SH2 domain-containing COOH-terminal fragment of Vav inhibited Vav phosphorylation and movement to the GEMs but had no effect on the tyrosine phosphorylation of the adaptor protein, SLP-76 (SH2 domain-containing leukocyte protein of 76 kD), and LAT. However, assembly of the multiprotein complex containing these proteins was inhibited. In addition, FcinRI-dependent activation of c-Jun NH(2)-terminal kinase 1 (JNK1) was also inhibited. Thus, Vav localization to the plasma membrane is mediated by its SH2 domain and may serve to regulate downstream effectors like JNK1.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Ciclo Celular , Proteínas de Membrana , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas/fisiologia , Domínios de Homologia de src , Animais , Proteínas de Transporte/análise , Membrana Celular/química , Ativação Enzimática , Precursores Enzimáticos/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Quinases JNK Ativadas por Mitógeno , Camundongos , Fosfoproteínas/análise , Proteínas Tirosina Quinases/fisiologia , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas c-vav , Receptores de IgE/metabolismo , Quinase Syk , Proteínas rac1 de Ligação ao GTP/análiseRESUMO
AIM: A psychological behaviour management programme with information and communications technology was developed that includes symbolic modelling, tell-show-do, positive reinforcement and distraction, and provides real-time treatment information. We hypothesised that the programme would help patients feel less stressed and show less uncooperative behaviours and subjective pain. MATERIALS AND METHODS: Forty-eight paediatric patients were recruited from May 2016 to January 2017, and randomly divided into a control group and an experimental group. In the control, patients watched cartoon animations during the first and second treatments. The experimental group watched cartoon animations during the first treatment, and they used the programme during the second treatment. To measure stress, uncooperative behaviour and subjective pain, we recorded the heart rate, Procedure Behaviour Checklist (PBCL) and Wong and Baker's Faces Pain Rating Scale (FPRS). RESULTS: The experimental group resulted in a significantly lower mean heart rate, uncooperative behaviour and subjective pain in the second treatment than did the control group (p<0.001). The differences in heart rate and uncooperative behaviour between the treatments were also significantly greater in the experimental group than in the control group (p<0.001). CONCLUSION: The programme was effective in relieving fear and anxiety as well as learning cooperative behaviour.
Assuntos
Comportamento Infantil , Ansiedade ao Tratamento Odontológico , Criança , Comportamento Cooperativo , Ansiedade ao Tratamento Odontológico/prevenção & controle , Frequência Cardíaca , Humanos , DorRESUMO
Fudosteine is a novel mucoactive agent, although little is known about how fudosteine decreases mucin production. The present study examined the effects of fudosteine on MUC5AC mucin synthesis and cellular signalling. An animal model of lipopolysaccharide (LPS)-induced inflammation and a bronchial epithelial cell line model of tumour necrosis factor (TNF)-alpha-induced inflammation were used. Fudosteine was administered before stimulation with LPS or TNF-alpha. The MUC5AC mucin levels were assayed and the expression of the MUC5AC gene was measured. Western blotting was carried out for the detection of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated extracellular signal-related kinase (p-ERK). MUC5AC mucin synthesis and the expression of the MUC5AC gene were increased by LPS in rats or TNF-alpha in NCI-H292 cells; these effects were inhibited by fudosteine treatment. After stimulation with LPS or TNF-alpha, the expression of p-EGFR, p-p38 MAPK and p-ERK were detected. Fudosteine treatment reduced the expression levels of p-p38 MAPK and p-ERK in vivo and of p-ERK in vitro. The present results suggest fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of extracellular signal-related kinase and p38 mitogen-activated protein kinase in vivo and extracellular signal-related kinase in vitro.
Assuntos
Cistina/análogos & derivados , Mucina-5AC/química , Mucinas/metabolismo , Animais , Linhagem Celular Tumoral , Cistina/farmacologia , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Masculino , Modelos Biológicos , Mucina-5AC/biossíntese , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Mesangial cell extracellular matrix (ECM) synthesis plays an important role in chronic renal diseases including chronic renal allograft dysfunction and diabetic nephropathy. Although inosine monophosphate dehydrogenase 2 (IMPDH2), as a target of mycophenolic acid (MPA), is important for de novo guanosine synthesis in lymphocytes, mesenchymal cells are not wholly dependent on it. To explore the importance of IMPDH2 on the inhibitory effects of MPA in mesangial cells (MC), we compared the effects of MPA and IMPDH2 siRNA on high glucose (HG)-induced fibronectin secretion and cellular reactive oxygen species (ROS). Mouse mesangial cells (MMC) were stimulated with HG (30 mmol/L D-glucose) in the presence or absence of MPA pretreatment or IMPDH2 siRNA transfection. Fibronectin secretion was measured by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS assessed by flow cytometry. HG increased fibronectin secretion by 1.8-fold at 24 hours and DCF-sensitive cellular ROS by 1.5-fold at 1 hour. MPA at 10 micromol/L totally inhibited HG-induced fibronectin secretion and cellular ROS in MMC. However, IMPDH2 siRNA only partially suppressed HG-induced fibronectin secretion and cellular ROS. These results suggested that MPA may inhibit HG-induced fibronectin secretion partially through inhibiting cellular ROS and the inhibition of IMPDH2 may be partially involved in the mechanism of MPA.