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1.
Phys Rev Lett ; 116(16): 166102, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27152812

RESUMO

The small spin-orbit interaction of carbon atoms in graphene promises a long spin diffusion length and the potential to create a spin field-effect transistor. However, for this reason, graphene was largely overlooked as a possible spin-charge conversion material. We report electric gate tuning of the spin-charge conversion voltage signal in single-layer graphene. Using spin pumping from an yttrium iron garnet ferrimagnetic insulator and ionic liquid top gate, we determined that the inverse spin Hall effect is the dominant spin-charge conversion mechanism in single-layer graphene. From the gate dependence of the electromotive force we showed the dominance of the intrinsic over Rashba spin-orbit interaction, a long-standing question in graphene research.

2.
Public Health ; 139: 189-197, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27596483

RESUMO

OBJECTIVES: To clarify the frequency of musculoskeletal problems in public elementary and junior high school children and to determine the advantages and problems of musculoskeletal examinations. STUDY DESIGN: School-based cross-sectional study nested in a cohort. METHODS: We examined 41,376 public elementary and junior high school children (aged 6-15 years) in Miyazaki, Japan, from 2008 to 2014. Participation was voluntary. Participants received an in-school primary musculoskeletal examination (clinical examination with check items and a questionnaire) and a secondary examination at an orthopaedic outpatient clinic as indicated. Estimated prevalence rates for musculoskeletal problems were calculated from the results of both examinations. RESULTS: The total estimated prevalence of musculoskeletal problems was 8.6%. Prevalence by school grade ranged from 3.2% to 13.7%. Estimated prevalence rates increased as grade increased and were higher in junior high school students than in elementary school students. The secondary examination identified musculoskeletal problems on the back (65.4%), knee (8.1%), ankle or feet (7.3%) and elbow (5.4%). Of those referred for a secondary examination, 44.4% had not reported musculoskeletal complaints on the initial questionnaire. Overall, 69.8% of problems diagnosed in the secondary examination were previously undiagnosed. CONCLUSIONS: School-based musculoskeletal examination enables early detection of abnormal growth and disorders of the locomotive organs and is expected to support children's musculoskeletal growth and development. We recommend musculoskeletal examinations as part of school check-ups in Japan. Our findings suggest musculoskeletal examinations should be conducted for students in higher elementary school grades and for all junior high school students. Evaluation should include both direct clinical examination and questionnaires.


Assuntos
Programas de Rastreamento/métodos , Doenças Musculoesqueléticas/epidemiologia , Exame Físico , Serviços de Saúde Escolar , Estudantes/estatística & dados numéricos , Adolescente , Criança , Estudos de Coortes , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Japão/epidemiologia , Masculino , Prevalência , Inquéritos e Questionários
3.
Br J Cancer ; 111(12): 2308-15, 2014 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-25314067

RESUMO

BACKGROUND: Nucleostemin (NS) is essential for the maintenance of stem cell properties, the functions of which remain poorly understood in cancer cells. The purpose of this study was to explore the impact of NS on malignancy and its clinical significance in oral squamous cell carcinoma (OSCC) patients. METHODS: We investigated the effects of NS on the proliferation and invasion of OSCC using NS-overexpressing or -knockdown OSCC cells. We assessed the activation of the STAT3 (signal transducer and activator of transcription 3) signalling pathway and the downstream targets in the cells with different expression levels of NS. An immunohistochemical analysis of NS was also performed in 54 OSCC patients who were treated with preoperative chemoradiotherapy and surgery. RESULTS: The overexpression of NS significantly enhanced the proliferation and invasive potential of OSCC cells. On the other hand, downregulation of NS suppressed the invasiveness of the cells. The alterations of these malignant phenotypes were associated with the activation of STAT3 signalling and its downstream targets. An immunohistochemical analysis demonstrated that a high NS tumour expression level significantly correlated with an advanced T-stage and N-stage. Furthermore, a Cox regression analysis revealed that the NS status (hazard ratio, 9.09; P=0.002) was a significant progression factor for OSCC patients. CONCLUSIONS: Our results suggest that targeting NS may provide a promising treatment for highly malignant OSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Ligação ao GTP/biossíntese , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Bucais/metabolismo , Proteínas Nucleares/biossíntese , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células/fisiologia , Proteínas de Ligação ao GTP/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Neoplasias Bucais/genética , Proteínas Nucleares/genética , Fenótipo , Prognóstico , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Transfecção
4.
Int J Sports Med ; 35(12): 1012-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24838268

RESUMO

The present study aims to improve medical systems by designing objective safety assessment criteria for rugby competitions. We evaluated 195 competitions between 2002 and 2011 using an original safety scale comprising the following sections: 1) competence of staff such as referees, medical attendants and match day doctor; 2) environment such as weather, wet bulb globe temperature and field conditions; and 3) emergency medical care systems at the competitions. Each section was subdivided into groups A, B and C according to good, normal or fair degrees of safety determined by combinations of the results.Overall safety was assessed as A, B and C for 110, 78 and 7 competitions, respectively. The assessments of individual major factors were mostly favorable for staff, but the environment and medical care systems were assessed as C in 25 and 70, respectively, of the 195 competitions. Medical management involves not having a match day doctor, but also comprehensive management including preventive factors and responses from the staff, environment and medical-care systems. 6 cases of severe injuries and accidents occurred between 2002 and 2011, which were observed in Grade A competition. These cases revealed better prognosis without obvious impairment, thus confirming the value of the present assessment scale.


Assuntos
Traumatismos em Atletas/prevenção & controle , Gestão da Segurança , Futebol/lesões , Serviços Médicos de Emergência , Meio Ambiente , Humanos , Corpo Clínico , Papel do Médico , Estudos Prospectivos , Medicina Esportiva
5.
Br J Cancer ; 109(8): 2199-206, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24045667

RESUMO

BACKGROUND: The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown. METHODS: To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer. RESULTS: Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046). CONCLUSION: The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.


Assuntos
Proteínas Ribossômicas/metabolismo , Neoplasias Gástricas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Nucléolo Celular/genética , Nucléolo Celular/metabolismo , Progressão da Doença , Humanos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Ribossômicas/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genética
6.
Eur Surg Res ; 51(1-2): 91-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24157453

RESUMO

AIM: The aim of the present study was to clarify differences in node metastasis mode and clinical outcomes based on tumor location in patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Participants comprised 228 patients with ESCC who underwent radical esophagectomy without preoperative supplement therapies. Lymph nodes were harvested from three fields: the neck, thorax, and abdomen. Patients were divided into three groups depending on tumor location [upper esophagus (UE), middle esophagus, or lower esophagus (LE)] and analyzed clinicopathologically. RESULTS: The LE group showed significantly more progressive ESCC in terms of tumor invasion (p = 0.025), node metastasis (p = 0.0071), and TNM stage (p = 0.0043). The LE group revealed a tendency to metastasize to extrathoracic (especially abdominal) nodes (p = 0.0008). Recurrent laryngeal node metastasis was increased in the UE group (p = 0.016). However, no prognostic differences were detected between groups according to tumor location. Likewise, subgroup analyses by surgical approach (open thoracotomy vs. thoracoscopy) and cancer stage (stage I/II, III, and IV) did not reveal any significant prognostic impact of tumor location. CONCLUSION: Lymphatic spread varied by tumor location, but no prognostic impact of tumor location could be detected in patients with ESCC in spite of surgical approach or cancer stage.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
7.
Phys Rev Lett ; 109(18): 187603, 2012 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-23215331

RESUMO

Using electron paramagnetic resonance (EPR), energy levels of the carbon vacancy (V(C)) in 4H-SiC and its negative-U properties have been determined. Combining EPR and deep-level transient spectroscopy we show that the two most common defects in as-grown 4H-SiC--the Z(1/2) lifetime-limiting defect and the EH(7) deep defect--are related to the double acceptor (2-|0) and single donor (0|+) levels of V(C), respectively.

8.
Clin Exp Dermatol ; 37(3): 241-4, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22007878

RESUMO

Reiter disease (RD) is characterized by a triad of sterile arthritis, urethritis and conjunctivitis. The conditions occur concomitantly or sequentially, and are associated with mucocutaneous features such as circinate balanitis and stomatitis. Arthritis usually occurs in attacks followed by recovery, but it sometimes progresses to permanent damage of the affected joints. Because the symptoms of this disorder are attributable to activated neutrophils, we assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) in a 73-year-old man with RD who had skin rashes on his penis, scrotum and right hand, with severe arthralgia. The patient's skin rash and joint pain responded dramatically to five sessions of GCAP delivered at intervals of 5 days. We present a detailed description of the patient and discuss the mechanisms of GCAP, and suggest that GCAP may be useful for treating RD.


Assuntos
Artrite Reativa/terapia , Doenças dos Genitais Masculinos/terapia , Leucaférese/métodos , Dermatopatias Papuloescamosas/terapia , Adsorção , Idoso , Doenças dos Genitais Masculinos/etiologia , Humanos , Masculino , Dermatopatias Papuloescamosas/etiologia , Resultado do Tratamento
9.
Int J Oral Maxillofac Surg ; 51(12): 1510-1515, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35346543

RESUMO

Carcinoma of unknown primary (CUP) is defined as lymph node metastasis without a detectable origin until after the initial treatment has been performed. The most common occult primary site in the head and neck, as revealed by a review of the published literature, is the oropharynx. An occult primary site in the oral region is extremely rare. We report a rare case of head and neck CUP (HNCUP) in a 69-year-old female patient, wherein the occult primary lesion was a primary intraosseous carcinoma (PIOC) invading the anterior maxilla. During the course of the initial diagnostic workup, no primary lesion could be identified; however, cervical lymph node metastasis to left levels IB and IIA were observed in the patient. A neck dissection followed by adjuvant radiotherapy was performed. However, the PIOC of the anterior maxilla was identified 6 months after neck treatment and was confirmed as the occult primary tumour of the HNCUP. This case is quite rare and required a comprehensive workup to guide optimal treatment. Careful follow-up or active biopsy should be considered if osteolytic changes are observed in the jaw.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Primárias Desconhecidas , Humanos , Feminino , Idoso , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/terapia , Metástase Linfática , Maxila/patologia , Carcinoma de Células Escamosas/patologia , Esvaziamento Cervical
10.
Int J Tuberc Lung Dis ; 26(4): 310-316, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35351235

RESUMO

BACKGROUND: The presence of depressive symptoms in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) is an important research topic; however, the prevalence of depressive symptoms and the factors that influence their development are unclear.OBJECTIVE: To analyse the association between CES-D (Center for Epidemiological Studies Depression Scale) scores and clinical parameters such as age, disease duration, pulmonary function, imaging findings, blood data, physical functions, sleep disturbances, respiratory symptoms and health-related quality of life (HRQOL).METHODS: We conducted a cross-sectional retrospective study of 114 patients with NTM-PD at a single centre from March 2016 to January 2021 to evaluate the relationship between CES-D scores and clinical parameters.RESULTS: Participants had a median age of 64 years; 32.5% of them had depressive symptoms. Disease duration, albumin, C-reactive protein, pulmonary function, dyspnoea, exercise capacity, respiratory symptoms, cough-related HRQOL and sleep disturbances were associated with depressive symptoms. Binomial logistic regression analyses indicated that the CES-D score was significantly associated with cough-related HRQOL and sleep disturbances.CONCLUSION: A high percentage of NTM-PD patients in this study experienced depressive symptoms, and these patients had abnormalities of various clinical parameters. Cough-related HRQOL and sleep disturbance had a strong influence on the development of depressive symptoms.


Assuntos
Pneumopatias , Micobactérias não Tuberculosas , Tosse , Estudos Transversais , Depressão/epidemiologia , Humanos , Pneumopatias/epidemiologia , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários
11.
Br J Cancer ; 105(9): 1322-30, 2011 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-21952624

RESUMO

BACKGROUND: Resistance to 5-fluorouracil (5-FU) is a major obstacle in treating oral squamous cell carcinoma (OSCC). However, little is known about apoptosis resistance, which contributes to 5-FU resistance in OSCC. METHODS: We focussed on the cellular inhibitor of apoptosis protein 2 (cIAP2) on the basis of a DNA microarray data using parental and 5-FU-resistant OSCC cell lines. The effects of cIAP2 downregulation on 5-FU sensitivity and apoptosis were evaluated. An immunohistochemical analysis of cIAP2 and related proteins, cIAP1 and X-linked IAP, was performed in 54 OSCC patients who were treated with 5-FU-based chemoradiotherapy and surgery. RESULTS: The downregulation of cIAP2 significantly enhanced the sensitivity of the 5-FU-resistant cells to 5-FU, with a significant increase in apoptosis. The immunohistochemical analysis demonstrated a high cIAP2 tumour expression to significantly correlate with the pathological response to chemoradiotherapy. Furthermore, a Cox regression analysis revealed the cIAP2 expression status (hazard ratio, 4.91; P=0.037) and the pathological response to chemoradiotherapy (hazard ratio, 0.418; P=0.016) to be significant prognostic factors for OSCC patients. CONCLUSION: These novel findings demonstrate that cIAP2 may represent a potentially useful therapeutic target for improving the treatment and survival of OSCC patients, particularly in the setting of 5-FU resistance.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/uso terapêutico , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Bucais/metabolismo , Apoptose , Proteína 3 com Repetições IAP de Baculovírus , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Quimiorradioterapia , Fluoruracila/farmacologia , Humanos , Prognóstico , Ubiquitina-Proteína Ligases , Regulação para Cima
12.
Br J Cancer ; 104(2): 376-86, 2011 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-21063397

RESUMO

BACKGROUND: The aim of this study is to find a novel molecular target based on chromosomal alteration and array-based gene expression analyses in bladder cancer (BC). We investigated a cancer testis antigen, LY6K, which is located on chromosome 8q24.3. METHODS: Five BC cell lines were subjected to high-resolution array-comparative genomic hybridisation with 244 000 probes. The expression levels of LY6K mRNA were evaluated in BC cell lines and clinical BC specimens by real-time reverse transcription-PCR. The cell lines were subjected to fluorescence in situ hybridisation of LY6K. Cell viability was evaluated by cell growth, wound healing, and matrigel invasion assays. RESULTS: Typical gained loci (P<0.0001) at 6p21.33-p21.32, 8q24.3, 9q34.13, 11q13.1-q14.1, 12q13.12-q13.13, 16p13.3, and 20q11.21-q13.33 were observed in all of the cell lines. We focused on 8q24.3 locus where LY6K gene harbours, and it was the top upregulated one in the gene profile from the BC cell line. LY6K mRNA expression was significantly higher in 91 BCs than in 37 normal bladder epitheliums (P<0.0001). Fluorescence in situ hybridisation validated that the high LY6K mRNA expression was due to gene amplification in the region where the gene harbours. Cell viability assays demonstrated that significant inhibitions of cell growth, migration, and invasion occured in LY6K knock down BC cell lines; converse phenomena were observed in a stable LY6K transfectant; and LY6K knockdown of the transfectant retrieved the original phenotype from the LY6K transfectant. CONCLUSION: Upregulation of the oncogenic LY6K gene located on the gained locus at 8q24.3 may contribute BC development.


Assuntos
Antígenos Ly/genética , Genoma Humano , Neoplasias da Bexiga Urinária/genética , Mapeamento Cromossômico , Proteínas Ligadas por GPI/genética , Técnicas de Silenciamento de Genes , Humanos , Hibridização in Situ Fluorescente , Invasividade Neoplásica , Metástase Neoplásica , RNA Mensageiro/genética , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Bexiga Urinária/patologia
13.
Int J Tuberc Lung Dis ; 25(4): 299-304, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33762074

RESUMO

BACKGROUND: Previous studies have shown a reduction in health-related quality of life (HRQoL) in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). However, the causes of this decline and the factors that contribute to it are unknown. This study was conducted to analyse the association between the St George´s Respiratory Questionnaire (SGRQ) and clinical parameters, including age, disease duration, body composition, pulmonary function, chest X-ray findings, blood data and physical function.METHODS: We performed a single-centre, cross-sectional, retrospective study of 101 patients with NTM-PD from December 2016 to October 2019. The relationship between the SGRQ scores and clinical parameters was evaluated.RESULTS: The median patient age was 67.0 years. Pulmonary function, radiological score, albumin levels, C-reactive protein levels and incremental shuttle walk test distance (ISWD) were significantly correlated with the total and component scores on the SGRQ. Multiple regression analysis showed that the SGRQ score was significantly associated with radiological score, pulmonary function and ISWD.CONCLUSION: This study was the first to assess the effect of clinical parameters on the SGRQ in patients with NTM-PD. HRQoL as determined using the SGRQ was associated with the radiological score, pulmonary function and ISWD in patients with NTM-PD.


Assuntos
Pneumopatias , Doença Pulmonar Obstrutiva Crônica , Idoso , Estudos Transversais , Humanos , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e Questionários
14.
Br J Cancer ; 102(5): 883-91, 2010 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-20160723

RESUMO

BACKGROUND: We have recently identified down-regulated microRNAs including miR-145 and miR-133a in bladder cancer (BC). The aim of this study is to determine the genes targeted by miR-145, which is the most down-regulated microRNA in BC. METHODS: We focused on fascin homologue 1 (FSCN1) from the gene expression profile in miR-145 transfectant. The luciferase assay was used to confirm the actual binding sites of FSCN1 mRNA. Cell viability was evaluated by cell growth, wound-healing, and matrigel invasion assays. BC specimens were subjected to immunohistochemistry of FSCN1 and in situ hybridisation of miR-145. RESULTS: The miR-133a as well as miR-145 had the target sequence of FSCN1 mRNA by the database search, and both microRNAs repressed the mRNA and protein expression of FSCN1. The luciferase assay revealed that miR-145 and miR-133a were directly bound to FSCN1 mRNA. Cell viability was significantly inhibited in miR-145, miR-133a, and si-FSCN1 transfectants. In situ hybridisation revealed that miR-145 expression was markedly repressed in the tumour lesion in which FSCN1 was strongly stained. The immunohistochemical score of FSCN1 in invasive BC (n=46) was significantly higher than in non-invasive BC (n=20) (P=0.0055). CONCLUSION: Tumour suppressive miR-145 and miR-133a directly control oncogenic FSCN1 in BC.


Assuntos
Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/fisiologia , Proteínas dos Microfilamentos/genética , Proteínas Supressoras de Tumor/fisiologia , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Luciferases/metabolismo , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica , Transfecção , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/prevenção & controle
15.
Int J Immunopathol Pharmacol ; 23(1): 105-19, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20377999

RESUMO

1,5-anhydroglucitol (1,5-AG) decreases in diabetic patients and is used as a marker of glycemic control. Type 2 diabetic patients are susceptibile to lipopolysaccharides (LPS), which stimulate macrophages to release large quantities of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. This study examines the effects of 1,5-AG on lung inflammation induced by LPS and consequent systemic inflammation to determine whether the decrease of 1,5-AG concentration induces susceptibility to LPS. Before the challenge with LPS (1 mg/kg in vivo and 500 ng/ml in vitro), we pretreated db/db mice and RAW264.7 cells with 1,5-AG at 38.5 mg/kg and 500 microg/ml, respectively. The levels of IL-6, TNF-alpha, macrophage chemoattractant protein (MCP)-1 and IL-1beta in the serum and in the cell supernatants were measured. We also measured macrophage recruitment and the expression of inducible nitric oxide synthase (iNOS) in pulmonary tissues. We found that 1,5-AG attenuated serum cytokine release and protected db/db mice from LPS-induced pulmonary inflammation. In addition, 1,5-AG suppressed cytokine release and iNOS expression by suppressing Akt/NF-kB activity in RAW264.7 cells. These results suggest that 1,5-AG may be a mediator in, as well as marker for diabetes, and 1,5-AG intake may confer tolerance to LPS in patients with type 2 diabetes.


Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/antagonistas & inibidores , Desoxiglucose/farmacologia , Diabetes Mellitus Tipo 2/imunologia , Animais , Glicemia/análise , Linhagem Celular , Citocinas/biossíntese , DNA/metabolismo , Desoxiglucose/sangue , Macrófagos Alveolares/efeitos dos fármacos , Masculino , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/biossíntese , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo
16.
J Pathol ; 216(4): 471-82, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18798223

RESUMO

Genomic copy number aberrations (CNAs) are believed to play a major role in the development and progression of human cancers. Although many CNAs have been reported in gastric cancer, their genome-wide transcriptional consequences are poorly understood. In this study, to reveal the impact of CNAs on genome-wide expression in gastric cancer, we analysed 30 cases of gastric cancers for their CNAs by array comparative genomic hybridization (array CGH) and 24 of these 30 cases for their expression profiles by oligonucleotide-expression microarray. We found that with the application of laser microdissection, most CNAs were detected at higher frequency than in previous studies. Notably, gain at 20q13 was detected in almost all cases (97%), suggesting that this may play an important role in the pathogenesis of gastric cancer. By comparing the array CGH data with expression profiles of the same samples, we showed that both genomic amplification and deletion strongly influence the expression of genes in altered genomic regions. Furthermore, we identified 125 candidate genes, consisting of 114 up-regulated genes located in recurrent regions (>10%) of amplification and 11 down-regulated genes located in recurrent regions of deletion. Up-regulation of several candidate genes, such as CDC6, SEC61G, ANP32E, BYSL and FDFT1, was confirmed by immunohistochemistry. Interestingly, some candidate genes were localized at genomic loci adjacent to well-known genes such as EGFR, ERBB2 and SMAD4, and concordantly deregulated by genomic alterations. Based on these results, we propose that our list of candidate genes may contain novel genes involved in the pathogenesis of advanced gastric cancer.


Assuntos
Aberrações Cromossômicas , Hibridização Genômica Comparativa/métodos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Dosagem de Genes , Expressão Gênica , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
17.
Sci Adv ; 5(2): eaau3407, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30746485

RESUMO

The distribution of defects and dislocations in graphene layers has become a very important concern with regard to the electrical and electronic transport properties of device applications. Although several experiments have shown the influence of defects on the electrical properties of graphene, these studies were limited to measuring microscopic areas because of their long measurement times. Here, we successfully imaged various local defects in a large area of chemical vapor deposition graphene within a reasonable amount of time by using lock-in thermography (LIT). The differences in electrical resistance caused by the micrometer-scale defects, such as cracks and wrinkles, and atomic-scale domain boundaries were apparent as nonuniform Joule heating on polycrystalline and epitaxially grown graphene. The present results indicate that LIT can serve as a fast and effective method of evaluating the quality and uniformity of large graphene films for device applications.

18.
J Cell Physiol ; 217(2): 338-49, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18543247

RESUMO

Aquaporin 3 (AQP3) is the predominant water channel protein in human keratinocytes and acts as an inflammatory mediator in some lesions. A chronic, inflammatory process of periodontitis is related with a dramatic change of surrounding fluid homeostasis to plasma extravasation. The exact pattern of aquaporin (AQP) water channel expression and its mechanism in periodontal disease is still unknown. We describe herein an up-regulated AQP3 expression in the epithelial lesion with chronic periodontitis and its functional role. The levels of AQP3 expression in inflamed gingival epithelial tissues were significantly higher than those of healthy subjects. Consistent with these results, AQP3 expression (i.e., levels of mRNA and protein) in cultured rat primary gingival epithelial cells and the human gingival epithelial cell line Ca9-22 were strongly increased in response to TNF-alpha treatment through the 55 kDa TNF-alpha receptor (TNFR I). In this context, small interfering RNA- (siRNA)-mediated "aqp-3 gene silencing," which could reduce AQP3 expression by more than 65%, significantly attenuated selected proinflammatory events of ICAM-1 expression induced by TNF-alpha in Ca9-22. A sixfold increase in leukocyte adherence to TNF-alpha-stimulated epithelial cells was demonstrated by an adherence assay (P < 0.001) and pretreatment with AQP3 siRNA and anti-ICAM-1 antibody reduced leukocyte retention by 85% (P < 0.001). Our study indicates for the first time a novel important mode in the regulation of the inflammatory response through TNF-alpha/TNFR I ligation at the site of epithelial lesions by specialized membrane channel AQP3 and ICAM-1 protein, which is closely implicated in the development of periodontitis mechanisms.


Assuntos
Aquaporina 3/metabolismo , Células Epiteliais/metabolismo , Gengiva/metabolismo , Periodontite/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Aquaporina 3/genética , Adesão Celular , Linhagem Celular , Doença Crônica , Células Epiteliais/imunologia , Feminino , Gengiva/imunologia , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Periodontite/imunologia , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Proteínas Recombinantes/metabolismo , Fatores de Tempo , Transfecção , Regulação para Cima
19.
J Periodontal Res ; 43(1): 76-83, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18067550

RESUMO

BACKGROUND AND OBJECTIVE: High-mobility-group box 1 functions as a late-phase inflammatory mediator. It can be released extracellularly by macrophages and necrotic cells through lipopolysaccharide and tumor necrosis factor-alpha. The objective of this study was to clarify the source of high-mobility-group box 1 in chronic periodontitis tissues and tumor necrosis factor-alpha-stimulated gingival epithelial cells, and subsequently elucidate its inducible inflammatory pathway. MATERIAL AND METHODS: Chronic periodontitis and healthy gingival sections were stained for high-mobility-group box 1 by immunohistochemistry and immunofluorescence. The amounts of high-mobility-group box 1 released into the gingival crevicular fluid and supernatants from gingival epithelial cells stimulated by tumor necrosis factor-alpha were examined by western blot. The phosphorylation of mitogen-activated protein kinases (MAPKs) in gingival epithelial cells was also examined. RESULTS: High-mobility-group box 1 was detected in the cytoplasm and nucleus of gingival epithelial cells with periodontitis. Western blotting revealed a significant increase in high-mobility-group box 1 expression in the gingival crevicular fluid from periodontitis patients. High-mobility-group box 1 production in gingival epithelial cells was increased following stimulation with tumor necrosis factor-alpha. The molecular dialogue between tumor necrosis factor-alpha and gingival epithelial cells involved modulation of the activities of p38MAPK, Jun N-terminal kinase and p44/42. Interestingly, only phosphorylation of p38MAPK contributed to more than half of the signaling initiated by tumor necrosis factor-alpha-elicited high-mobility-group box 1 release. CONCLUSION: High-mobility-group box 1 is continuously released from the gingival epithelial cells modulated by tumor necrosis factor-alpha. These findings imply that high-mobility-group box 1 expression and possibly p38MAPK constitute important features in periodontitis.


Assuntos
Células Epiteliais/efeitos dos fármacos , Gengiva/efeitos dos fármacos , Proteína HMGA1a/metabolismo , Periodontite/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Animais , Estudos de Casos e Controles , Sobrevivência Celular , Células Epiteliais/metabolismo , Feminino , Gengiva/citologia , Líquido do Sulco Gengival/química , Proteína HMGA1a/análise , Humanos , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/análise , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno/análise , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Clin Oncol (R Coll Radiol) ; 20(2): 148-51, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17851056

RESUMO

AIMS: p53AIP1 is a potential mediator of p53-dependent apoptosis that is mutated in many kinds of carcinoma. To investigate the role of this gene for non-small cell lung cancer, we compared the relationship between p53AIP1 gene expression and clinicopathological status of lung cancer. MATERIALS AND METHODS: Seventy samples from non-small cell lung cancer patients were obtained between 1997 and 2003. For quantitative evaluation of RNA expression by polymerase chain reaction (PCR) we used the Taqman PCR methods. Exons 5-8 of the p53 gene were analysed using PCR-single-stranded conformation polymorphism and sequenced for mutation analysis. RESULTS: p53AIP1 gene expression levels in the lymph node metastasis-positive group were significantly lower than in the negative group (positive 35.1+/-83.9; negative 64.2+/-113.4; P=0.0486). The overall survival of the p53AIP1 low expression group was significantly worse than that of the p53AIP1 high expression group (P=0.0206). In the multivariate Cox proportional hazard model, p53AIP1 (P=0.0489) was the independent predictor for overall survival. When we investigated mutation analyses of the p53 gene, we could find several point mutations in 15.7% of all samples. However, there was no relationship between p53AIP1 expression and p53 status. CONCLUSIONS: These data suggest that the p53AIP1 gene is important for non-small cell lung cancer progression and may be a possible prognostic marker.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Genes p53 , Neoplasias Pulmonares/genética , Idoso , Apoptose , Feminino , Expressão Gênica , Humanos , Metástase Linfática , Masculino , Mutação , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Prognóstico , Fumar/efeitos adversos , Análise de Sobrevida
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