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1.
Br J Surg ; 105(10): 1349-1358, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29741294

RESUMO

BACKGROUND: Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The aim of this study was to identify molecules responsible for mediating peritoneal metastasis of gastric cancer. METHODS: Transcriptome and bioinformatics analyses were conducted to identify molecules associated with peritoneal metastasis. The therapeutic effects of intraperitoneally administered small interfering (si) RNA were evaluated using mouse xenograft models. Expression of mRNA and protein was determined in gastric tissues from patients with gastric cancer. RESULTS: Synaptotagmin XIII (SYT13) was expressed at significantly higher levels in patients with peritoneal recurrence, but not in those with hepatic or distant lymph node recurrence. Inhibition of SYT13 expression in a gastric cancer cell line transfected with SYT13-specific siRNA (siSYT13) was associated with decreased invasion and migration ability of the cells, but not with proliferation and apoptosis. Intraperitoneal administration of siSYT13 significantly inhibited the growth of peritoneal nodules and prolonged survival in mice. In an analysis of 200 patients with gastric cancer, SYT13 expression in primary gastric cancer tissues was significantly greater in patients with peritoneal recurrence or metastasis. A high level of SYT13 expression in primary gastric cancer tissues was an independent risk factor for peritoneal recurrence. CONCLUSION: SYT13 expression in gastric cancer is associated with perioneal metatases and is a potential target for treatment.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Sinaptotagminas/metabolismo , Idoso , Animais , Biomarcadores Tumorais/antagonistas & inibidores , Linhagem Celular Tumoral , Biologia Computacional , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Transplante de Neoplasias , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/prevenção & controle , Interferência de RNA , RNA Interferente Pequeno/uso terapêutico , Terapêutica com RNAi , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Sinaptotagminas/antagonistas & inibidores , Transcriptoma
2.
Cell Mol Biol (Noisy-le-grand) ; 62(12): 74-78, 2016 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-27894404

RESUMO

Streptozotocin (STZ), a naturally occurring chemical, is toxic to the various kinds of cells such as insulin-producing beta cells. However, the beneficial effect of STZ on neuronal cells such as neurite outgrowth-inducing activity has been unknown. In this study, we examined the effect of STZ on neurite outgrowth in mouse neuronal Neuro2a cells. STZ (0.01 mM~5 mM) exerted remarkable neurite outgrowth-inducing activity in Neuro2a cells in a concentration dependent manner. STZ also had the same neurite outgrowth-inducing activity as that of retinoic acid (RA), which is well known neurite outgrowth inducer. As with the result of RA treatment, STZ administration increased MAP2-positive cells. The MAP2-positive cells reflect neurite outgrowth-induced cells. STZ (0.01 mM~5 mM) did not induce cell death, but significantly decreased cell proliferation. The serine/threonine kinase Akt, a downstream target of phosphatidylinositol-3 kinase (PI3K), was transiently phosphorylated at Ser473 and at Thr303 by STZ (5 mM) administration. Glycogen synthase kinase 3ß (GSK3ß), which has been reported to be inactivated by Akt, was also transiently phosphorylated at Ser9 by STZ (5 mM) administration. In addition, a blocker of PI3K, LY294002 (10 µM), significantly attenuated STZ-induced neurite outgrowth. These results suggest that STZ induces neurite outgrowth via activation of PI3K-Akt signaling pathway and GSK3ß inhibition.


Assuntos
Glicogênio Sintase Quinase 3 beta/metabolismo , Crescimento Neuronal/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Immunoblotting , Camundongos , Morfolinas/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos
3.
Dis Esophagus ; 29(6): 598-602, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26338205

RESUMO

Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Esofagectomia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias Laríngeas/terapia , Laringectomia , Neoplasias Primárias Múltiplas/terapia , Neoplasias Faríngeas/terapia , Faringectomia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Carcinoma de Células Escamosas do Esôfago , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos , Terapia de Salvação , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
4.
Dis Esophagus ; 29(6): 663-9, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25951896

RESUMO

Despite improvements in surgical techniques, perioperative management, and multidisciplinary therapy, treatment outcomes of patients with esophageal squamous cell carcinoma (ESCC) remain poor. Therefore, development of novel molecular biomarkers, which either predict patient survival or become therapeutic targets, is urgently required. In the present study, to facilitate early detection of ESCC and predict its clinical course, we investigated the relationship of the serum level of melanoma-associated antigen (MAGE)-D4 to patients' clinicopathological characteristics. Using quantitative real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays, we determined the levels of MAGE-D4 mRNA and protein in cell lysates and conditioned medium of cultures, respectively, of nine ESCC cell lines. Further, we determined MAGE-D4 levels in serum samples collected from 44 patients with ESCC who underwent radical esophagectomy without neoadjuvant therapy as well as from 40 healthy volunteers. Samples of conditioned medium and cell lysates contained comparable levels of MAGE-D4 that correlated closely with the levels of MAGE-D4 mRNA. Preoperative MAGE-D4 levels in the sera of 44 patients with ESCC, which varied from 0 to 2,354 pg/mL (314 ± 505 pg/mL, mean ± standard deviation), were significantly higher compared with those of healthy volunteers. By setting the cutoff at the highest value for healthy volunteers (50 pg/mL), the MAGE-D4-positive group of patients was more likely to have shorter disease-specific and disease-free survival compared with those of the MAGE-D4-negative group, although the differences were not statistically significant. Our results indicate that the elevation of preoperative serum MAGE-D4 levels in some patients with ESCC was possibly caused by excess production of MAGE-D4 by tumor cells followed by its release into the circulation. Clinical implications of serum MAGE-D4 levels should be validated in a large population of patients with ESCC.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirurgia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
5.
Dis Esophagus ; 28(2): 188-95, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24147998

RESUMO

To pursue an urgently needed treatment target for esophageal cancer (EC), we investigated the function of the recently discovered melanoma-associated antigen (MAGE)-D4 in squamous cell EC. MAGE-D4 messenger RNA (mRNA) expression was analyzed in nine EC cell lines using quantitative reverse transcription polymerase chain reaction. In 65 surgical specimens of squamous cell EC with no prior neoadjuvant therapy, MAGE-D4 mRNA expression in EC tissues and corresponding normal tissues was analyzed and compared, and evaluated in terms of clinicopathological factors. In representative cases, MAGE-D4 protein distribution was analyzed immunohistochemically. The heterogeneity of MAGE-D4 mRNA expression was confirmed in EC cell lines by quantitative reverse transcription polymerase chain reaction. In surgical specimens, MAGE-D4 mRNA expression was significantly higher in EC tissues than in corresponding normal tissues (P < 0.001). Patients with the highest MAGE-D4 mRNA expression in EC tissues (top quartile, n = 17) had significantly shorter overall survival than patients with low expression (2-year survival: 44% and 73%, respectively, P = 0.006). Univariate analysis identified age (≥65 years), lymphatic involvement, and high MAGE-D4 mRNA expression as significant prognostic factors; high MAGE-D4 mRNA expression was also an independent prognostic factor in multivariable analysis (hazard ratio: 2.194; P = 0.039) and was significantly associated with Brinkman index (P = 0.008) and preoperative carcinoembryonic antigen level (P = 0.002). Immunohistochemical MAGE-D4b expression was consistent with MAGE-D4 mRNA profiling. Our results suggest that MAGE-D4 overexpression influences tumor progression, and MADE-D4 can be a prognostic marker and a potential molecular target in squamous cell EC.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , RNA Mensageiro/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Progressão da Doença , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
6.
Br J Surg ; 100(13): 1791-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24227366

RESUMO

BACKGROUND: Peritoneal lavage cytology (CY) is used in the diagnosis and staging of various cancers. The clinical significance of positive cytology results in patients with pancreatic cancer is yet to be determined. METHODS: Peritoneal washing samples were collected from consecutive patients with pancreatic cancer between July 1991 and December 2012. The correlations between cytology results, clinicopathological parameters and recurrence patterns were evaluated. The prognostic impact of CY status, regarding resectability and the effectiveness of adjuvant chemotherapy, were analysed. RESULTS: Of 523 included patients, 390 underwent resection. Patients with tumours at least 2 cm in diameter were more likely to have CY+ status than patients with tumours smaller than 2 cm (48 of 312 versus 3 of 78 respectively; P = 0·005) and there was a significant correlation between CY+ status and tumour invasion of the anterior pancreatic capsule (43 of 276 versus 8 of 113 with no invasion of the capsule; P = 0·030). Although the overall survival of patients with resected CY+ tumours was worse than that of patients with resected CY- tumours, it was significantly better than the survival of unresected patients regardless of CY status. Multivariable analysis of all patients who had pancreatectomy did not identify CY+ as an independent prognostic factor. Patients with CY+ tumours tended to develop peritoneal metastasis more often than those with CY- tumours, although not significantly so. The median survival time of 34 patients with resected CY+ tumours who received adjuvant chemotherapy was better than that of 17 patients who had surgery alone, although this was not statistically significant (15·3 versus 10·0 months; P = 0·057). CONCLUSION: CY+ status is not clinically equivalent to gross peritoneal metastasis in patients with pancreatic cancer. Curative resection is still recommended regardless of CY status.


Assuntos
Neoplasias Pancreáticas/patologia , Lavagem Peritoneal/métodos , Peritônio/patologia , Quimioterapia Adjuvante , Citodiagnóstico/métodos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Peritoneais/secundário
7.
J Surg Oncol ; 105(4): 381-6, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22052684

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem, and identification of new tumor-related genes is an urgent task. METHODS: To detect tumor-related genes effectively, we performed double-combination array analysis, which consisted of an expression array and a single nucleotide polymorphism (SNP) array of a single surgical HCC specimen. RESULTS: Expression array analysis identified AKAP12 as one of the genes with reduced expression in HCC tissues when compared with non-cancerous adjacent hepatic tissues. In addition, AKAP12 expression levels in tumor tissues from 48 HCC samples were significantly lower (P < 0.001) than those in normal tissues, and the downregulation was significantly correlated with poor overall survival rate (P = 0.003). However, SNP array analysis revealed that locus 6q24-q25 where AKAP12 was located did not show chromosomal deletion. In contrast, hypermethylation in the AKAP12 promoter regions was observed in 41 of 48 HCC samples. We then confirmed that AKAP12 gene re-expression occurs after 5-aza-2'-deoxycytidine (5-aza-dC) treatment through direct sequence analysis of the AKAP12 promoter region in HCC cell lines. CONCLUSIONS: The current data suggest that AKAP12 is downregulated in cancer tissues through promoter hypermethylation, and may have a role as a candidate tumor suppressor gene for HCC.


Assuntos
Proteínas de Ancoragem à Quinase A/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Neoplasias Hepáticas/genética , Proteínas de Ancoragem à Quinase A/metabolismo , Adulto , Idoso , Apoptose , Azacitidina/análogos & derivados , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Metilação de DNA , Decitabina , Feminino , Perfilação da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida
8.
Diabet Med ; 28(10): 1221-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21658121

RESUMO

AIMS: To investigate whether a reduced incidence of cardiovascular disease in Type 2 diabetes can be achieved in a newly recruited cohort following the recently advanced concept of multifactorial treatment and followed in primary care settings as compared with earlier cohorts. METHODS: A prospective study was performed in primary care settings at multiple clinics nationwide in the Japan Diabetes Clinical Data Management (JDDM) study group. Subjects were 2984 patients with Type 2 diabetes without prevalent cardiovascular disease. The main outcome measure was the first event of non-fatal or fatal coronary heart disease, ischaemic stroke or peripheral artery disease, and the incidence was compared with other representative cohorts. RESULTS: There were 90 cardiovascular events over 10,827 person-years of follow-up with a dropout rate of 6%. The incidences (per 1000 person-years, 95% confidence interval) of composite, coronary heart disease, ischaemic stroke and peripheral artery disease in the JDDM study were 8.3 (6.6-10.0), 4.4 (3.2-5.6), 3.1 (2.1-4.2), and 0.7 (0.2-1.2), respectively. Each incidence was lowest in the JDDM study compared with other cohorts (P < 0.01 vs. each cohort). In the JDDM study, significant variables predictive of the occurrence of a cardiovascular event were age, duration of diabetes, HbA(1c), HDL cholesterol and urinary albumin. CONCLUSION: The novel finding of low cardiovascular disease occurrence in this study may be conferred by the feasibility at primary care settings for providing patients with Type 2 diabetes with favourable control of blood glucose, blood pressure and lipids, coupled with unique ethnicity/country factors.


Assuntos
Povo Asiático/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Atenção Primária à Saúde , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia
9.
Clin Exp Immunol ; 159(3): 315-26, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20015272

RESUMO

We have demonstrated previously that, in primary Sjögren's syndrome (SS), immature myeloid dendritic cells (DCs) are decreased in blood and mature myeloid DCs are accumulated in salivary glands, suggesting recruitment of the myeloid DCs from blood to salivary glands. To verify whether this finding is universal in patients of not only primary SS but also secondary SS, in this study we analysed the blood DCs of secondary SS patients. We examined 24 secondary SS and 29 primary SS patients. A direct correlation between the decreased number of myeloid DCs and the duration of Sicca syndrome in primary and secondary SS was observed; namely, the reduction of myeloid DCs in blood was restored spontaneously with duration time of Sicca syndrome. We also examined the immunohistochemical staining of salivary glands of SS patients with monoclonal antibodies against fascin, CD11c and human leucocyte antigen DR (HLA-DR). Fascin(+) or CD11c(+)/HLA-DR(+) mononuclear cells were present in the salivary glands of secondary SS patients, as in primary SS. However, fascin(+) mononuclear cells were barely detected in the salivary glands of a chronic phase of SS patients. We also found a negative correlation between the frequency of blood myeloid DCs and salivary gland-infiltrating DCs in secondary SS patients, as well as primary SS. Our results suggest that the reduction of blood myeloid DCs and preferential trafficking of myeloid DCs into salivary glands is a common event in the early stage of SS. Myeloid DCs may play essential roles in the pathogenesis of Sicca syndrome of SS by initiating T helper cell immune responses.


Assuntos
Células Dendríticas/imunologia , Células Mieloides/imunologia , Síndrome de Sjogren/imunologia , Adulto , Antígeno CD11c/imunologia , Antígeno CD11c/metabolismo , Proteínas de Transporte/imunologia , Proteínas de Transporte/metabolismo , Movimento Celular/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Feminino , Antígenos HLA-DR/imunologia , Antígenos HLA-DR/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Proteínas dos Microfilamentos/imunologia , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Células Mieloides/metabolismo , Células Mieloides/patologia , Glândulas Salivares/imunologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/patologia
10.
Cell Mol Biol (Noisy-le-grand) ; 56 Suppl: OL1447-52, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21215240

RESUMO

Preconditioning of sublethal ischemia implies a cytoprotective mechanism against subsequent ischemia­induced cell death; however, the precise mechanism by which preconditioning protects against ischemic injury is not known. In the present study, we clarified whether pretreatment with a sublethal concentration of H2O2 could counter subsequent H2O2-induced cytotoxicity and also investigated the mechanisms of the cytoprotective effect of a sublethal concentration of H2O2. Using the MTT reduction assay and Calcein-AM staining assay, we showed that pretreatment with H2O2 (10 µM, 24 hr) of COS7 cells partially protected cells against subsequent H2O2 (6 mM, 1 hr) - induced cytotoxicity. The phosphorylation of Akt/PKB, a downstream target of phosphatydylinositol-3 kinase (PI3K), at Ser473 was augmented by H2O2 (10 µM) administration. This augmentation peaked at 10 minutes after H2O2 (10 µM) treatment and fell to the basal level at 24 hr. A blocker of PI3K, LY294002, significantly attenuated H2O2 (10 µM, 24 hr) - induced cytoprotection. In addition, pretreatment with LY294002 reduced H2O2 (10 µM, 10 min)-induced phosphorylation of Akt at Ser473. These findings suggest that a sublethal concentration of H2O2 exerts a cytoprotective effect against subsequent H2O2-induced cell death and that this cytoprotective effect of H2O2 is mediated by activation of the PI3K-Akt signaling pathway.


Assuntos
Peróxido de Hidrogênio/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Apoptose , Células COS , Chlorocebus aethiops , Cromonas/química , Cromonas/farmacologia , Citoproteção/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Morfolinas/química , Morfolinas/farmacologia , Fosforilação , Fatores de Tempo
12.
Emerg Med J ; 26(7): 492-6, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19546269

RESUMO

BACKGROUND: Biphasic waveform defibrillation results in higher rates of termination of fibrillation than monophasic waveform defibrillation but has not been shown to improve survival outcomes. OBJECTIVE: To compare the effectiveness of a biphasic automated external defibrillator (AED) with a monophasic AED for witnessed out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF). METHODS: In a prospective population-based cohort study, adults with witnessed VF OHCA were treated with either monophasic or biphasic waveform AED shocks. The primary outcome measure was neurologically favourable 1-month survival, defined as a Cerebral Performance Categories score of 1 or 2. RESULTS: Of 366 adults with witnessed OHCA of presumed cardiac aetiology, 74 (20%) had VF. Termination of VF with the first shock tended to occur more frequently after biphasic AED shocks (36/44 (82%) vs 20/30 (67%), p = 0.14). Return of spontaneous circulation (ROSC) occurred more frequently after biphasic AED shocks (29/44 (66%) vs 8/30 (27%), p = 0.001). Neurologically favourable 1-month survival was also more frequent in the biphasic group (10/44 (23%) vs 1/30 (3%), p = 0.04). The median time interval from the first shock to the second shock was 67 s in the monophasic group and 24 s in the biphasic group (p = 0.001). CONCLUSIONS: Treatment with biphasic AED shocks improved the likelihood of ROSC and neurologically favourable 1-month survival after witnessed VF compared with monophasic AED shocks. In addition to waveform differences, a shorter time interval from the first shock to the second shock could account for the better outcomes with biphasic AED.


Assuntos
Desfibriladores , Cardioversão Elétrica/estatística & dados numéricos , Serviços Médicos de Emergência , Parada Cardíaca/terapia , Doenças do Sistema Nervoso/etiologia , Fibrilação Ventricular/terapia , Adulto , Idoso , Reanimação Cardiopulmonar/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
13.
AJNR Am J Neuroradiol ; 40(6): 1037-1042, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31122915

RESUMO

BACKGROUND AND PURPOSE: Reliable preoperative facial nerve mapping may help avoid or minimize facial nerve injury during parotid tumor resection. The purpose of this study was to investigate the diagnostic performance of the 3D double-echo steady-state with water excitation sequence in localizing parotid gland tumors through direct visualization of the intraparotid facial nerve in comparison with indirect methods of estimating the facial nerve location. MATERIALS AND METHODS: We retrospectively reviewed 91 parotid gland tumors in 90 patients who underwent surgical resection and preoperative MR imaging, including the 3D double-echo steady-state with water excitation sequence. The tumor locations were categorized as deep or superficial on the basis of direct and 3 indirect methods: the facial nerve line, retromandibular vein, and Utrecht line. Surgical localization was considered the criterion standard. The diagnostic performance for localizing deep lobe lesions using direct and indirect methods was calculated and compared using the McNemar test. RESULTS: Surgical localization confirmed 75 superficial lesions and 16 deep lesions. The interobserver variability of the 3D double-echo steady-state with water excitation sequence was excellent (κ = 0.870). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for localizing deep lobe lesions using the 3D double-echo steady-state with water excitation method were 97.8%, 87.5%, 100%, 100%, and 97.4%, respectively. These findings were significantly higher than the facial nerve line in sensitivity, the retromandibular vein in sensitivity, and the Utrecht line in accuracy and specificity (P < .05). Overall, the direct method was the most accurate, sensitive, and specific in localizing parotid gland tumors. CONCLUSIONS: We can achieve higher diagnostic performance in localizing parotid gland tumors by directly visualizing the intraparotid facial nerve using the 3D double-echo steady-state with water excitation sequence compared with indirect methods.


Assuntos
Nervo Facial/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Neoplasias Parotídeas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Parótida/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade , Água
14.
Br J Cancer ; 98(10): 1690-5, 2008 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-18475302

RESUMO

Alteration in transforming growth factor-beta signalling pathway is one of the main causes of pancreatic cancer. The human runt-related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including pancreatic cancer. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human pancreatic cancer. Thirty-two patients with pancreatic cancer were investigated in this study. We examined the methylation status of RUNX3 promoter region, loss of heterozygosity (LOH) at 1p36, and conducted a mutation analysis. The results were compared with clinicopathological data. Promoter hypermethylation was detected in 20 (62.5%) of 32 pancreatic cancer tissues, confirmed by sequence of bisulphite-treated DNA. Loss of heterozygosity was detected in 11 (34.3%) of 32 pancreatic cancers. In comparison with clinicopathological data, hypermethylation showed a relation with a worse prognosis (P=0.0143). Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in pancreatic cancer. Therefore, RUNX3 may be an important tumour suppressor gene related to pancreatic cancer.


Assuntos
Cromossomos Humanos Par 1 , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Inativação Gênica , Neoplasias Pancreáticas/genética , Adulto , Idoso , Metilação de DNA , Análise Mutacional de DNA , Epigênese Genética , Feminino , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/metabolismo , Polimorfismo Conformacional de Fita Simples , Valor Preditivo dos Testes , Prognóstico , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Análise de Sobrevida , Fator de Crescimento Transformador beta/metabolismo
15.
Anaesthesia ; 63(6): 635-40, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18477276

RESUMO

The Airtraq laryngoscope has an oropharyngeal airway-shaped blade that provides a non-line-of-sight view of the glottis. The configuration of the blade should mean that less movement of the cervical spine is required during laryngeal visualisation. We compared the degree of cervical spine movement in laryngoscopy performed using the Airtraq and conventional Macintosh laryngoscope. In 20 patients requiring general anaesthesia and tracheal intubation, we measured cervical spine movement using radiography in the same patient during consecutive procedures using the two laryngoscopes. Although significant movement of the cervical spine from baseline was noted during all procedures (p < 0.05), cervical spinal extension with the Airtraq was 29% less than that measured during Macintosh laryngoscopy between the occiput and C4, and 44% less at the C3/C4 motion segment (p < 0.05). Anterior deviations of the vertebral bodies from baseline were 32%, 35%, 38% and 40% less at the atlas, C2, C3, and C4 vertebrae, respectively, during Airtraq laryngoscopy than those measured during Macintosh laryngoscopy (p < 0.01). Our study demonstrated that laryngoscopy using the Airtraq laryngoscope involves less movement of the cervical spine compared to conventional procedures using a Macintosh laryngoscope.


Assuntos
Vértebras Cervicais/fisiologia , Laringoscópios , Movimento , Adulto , Anestesia Geral , Vértebras Cervicais/diagnóstico por imagem , Feminino , Movimentos da Cabeça , Humanos , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Laringoscopia , Pessoa de Meia-Idade , Radiografia
16.
Genes Brain Behav ; 17(5): e12435, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29057568

RESUMO

Atp1a3 is the Na-pump alpha3 subunit gene expressed mainly in neurons of the brain. Atp1a3-deficient heterozygous mice (Atp1a3+/- ) show altered neurotransmission and deficits of motor function after stress loading. To understand the function of Atp1a3 in a social hierarchy, we evaluated social behaviors (social interaction, aggression, social approach and social dominance) of Atp1a3+/- and compared the rank and hierarchy structure between Atp1a3+/- and wild-type mice within a housing cage using the round-robin tube test and barbering observations. Formation of a hierarchy decreases social conflict and promote social stability within the group. The hierarchical rank is a reflection of social dominance within a cage, which is heritable and can be regulated by specific genes in mice. Here we report: (1) The degree of social interaction but not aggression was lower in Atp1a3+/- than wild-type mice, and Atp1a3+/- approached Atp1a3+/- mice more frequently than wild type. (2) The frequency of barbering was lower in the Atp1a3+/- group than in the wild-type group, while no difference was observed in the mixed-genotype housing condition. (3) Hierarchy formation was not different between Atp1a3+/- and wild type. (4) Atp1a3+/- showed a lower rank in the mixed-genotype housing condition than that in the wild type, indicating that Atp1a3 regulates social dominance. In sum, Atp1a3+/- showed unique social behavior characteristics of lower social interaction and preference to approach the same genotype mice and a lower ranking in the hierarchy.


Assuntos
Inibidor da Ligação a Diazepam/farmacologia , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/fisiologia , Animais , Encéfalo/metabolismo , Inibidor da Ligação a Diazepam/genética , Inibidor da Ligação a Diazepam/metabolismo , Modelos Animais de Doenças , Heterozigoto , Relações Interpessoais , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Comportamento Social , Predomínio Social , Estresse Psicológico/genética , Transmissão Sináptica
17.
Mol Cell Biol ; 16(6): 2744-55, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8649382

RESUMO

SIT4 is the catalytic subunit of a type 2A-related protein phosphatase in Saccharomyces cerevisiae that is required for G1 cyclin transcription and for bud formation. SIT4 associates with several high-molecular-mass proteins in a cell cycle-dependent fashion. We purified two SIT4-associated proteins, SAP155 and SAP190, and cloned the corresponding genes. By sequence homology, we isolated two additional SAP genes, SAP185 and SAP4. Through such an association is not yet proven for SAP4, each of SAP155, SAP185, and SAP190 physically associates with SIT4 in separate complexes. The SAPs function positively with SIT4, and by several criteria, the loss of all four SAPs is equivalent to the loss of SIT4. The data suggest that the SAPs are not functional in the absence of SIT4 and likewise that SIT4 is not functional in the absence of the SAPs. The SAPs are hyperphoshorylated in cells lacking SIT4, raising the possibility that the SAPs are substrates of SIT4. By sequence similarity, the SAPs fall into two groups, the SAP4/SAP155 group and the SAP185/SAP190 group. Overexpression of a SAP from one group does not suppress the defects due to the loss of the other group. These findings and others indicate that the SAPs have distinct functions.


Assuntos
Proteínas Fúngicas/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Ciclo Celular/genética , Ciclo Celular/fisiologia , Clonagem Molecular , Primers do DNA/genética , DNA Fúngico/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Deleção de Genes , Expressão Gênica , Genes Fúngicos , Modelos Biológicos , Dados de Sequência Molecular , Fenótipo , Fosfoproteínas Fosfatases/química , Fosfoproteínas Fosfatases/genética , Conformação Proteica , Proteína Fosfatase 2 , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , Temperatura
18.
Transplant Proc ; 39(1): 160-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17275496

RESUMO

To recognize "normal" hepatic hemodynamics after live donor liver transplantation (LDLT), we analyzed Doppler parameters on recipients with a right liver graft and donors after extended left hepatectomy. Theoretically these values should be the same. From April 2000 to October 2004, 20 LDLTs were performed using a right liver graft. The 10 recipients without postoperative complications and their donors were included in this study. Portal venous velocity (PVV; cm/s), hepatic arterial peak systolic velocity (cm/s), and hepatic venous peak velocity (HVPV; cm/s) were measured during the first 2 weeks. In donors PVV and HVPV after LDLT were significantly higher after than before left hepatectomy: 19.2 +/- 4.2 vs. 31.5 +/- 13.0 cm/s (P = .013) and 23.0 +/- 7.2 vs. 41.8 +/- 10.3 cm/s respectively (P = .010). However, there were mild degrees of increased PVV and HVPV. In recipients, a markedly increased PVV (106.3 +/- 45.2 cm/s on day 1) was significantly higher than that in donors on each postoperative day. The hepatic arterial resistive index in recipients was also significantly higher than that in donors on each postoperative day, for example, 0.72 +/- 0.11 vs 0.62 +/- 0.04 on day 1 (P = .0326). In conclusion, we have shown "abnormal" hepatic hemodynamics in even those recipients without complications during the early postoperative period after LDLT.


Assuntos
Transplante de Fígado/fisiologia , Doadores Vivos , Período Pós-Operatório , Adulto , Velocidade do Fluxo Sanguíneo , Peso Corporal , Humanos , Fígado/anatomia & histologia , Fígado/diagnóstico por imagem , Circulação Hepática , Tamanho do Órgão , Sistema Porta , Ultrassonografia Doppler
19.
Kyobu Geka ; 59(3): 235-7, 2006 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-16528998

RESUMO

We report a rare case of isolated infectious tricuspid valve endocarditis. A 67-year-old male patient with chronic renal failure complained of fever up to 38 degrees C after hemodialysis. WBC was not elevated, but CRP was increased. Transthoracic and transesophageal echocardiography for investigating his chest discomfort demonstrated a large 13 x 25 mm vegetation on the tricuspid valve. Blood culture was negative. The tricuspid valve was replaced with a bioprosthetic valve. The extensive vegetation was found in the anterior, septal and posterior cusps and diagnosed as infectious endocarditis pathologically. The postoperative course was uneventful. WBC and CRP remained normal 9 months after surgery and no signs of recurrence were observed. The cause of the infectious endocarditis seemed to be the insertion of a double lumen catheter for dialysis or the puncture of the arteriovenous shunt.


Assuntos
Bioprótese , Endocardite Bacteriana/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Diálise Renal , Valva Tricúspide/cirurgia , Idoso , Endocardite Bacteriana/etiologia , Doenças das Valvas Cardíacas/etiologia , Humanos , Falência Renal Crônica/terapia , Masculino
20.
Nanoscale ; 8(21): 10956-62, 2016 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-27121127

RESUMO

We report a novel and facile self-limiting synthesis route of silicon nanocrystal (Si NC)-based colloidally stable semiconductor-metal (gold, silver and platinum) hybrid nanoparticles (NPs). For the formation of hybrid NPs, we employ ligand-free colloidal Si NCs with heavily boron (B) and phosphorus (P) doped shells. By simply mixing B and P codoped colloidal Si NCs with metal salts, hybrid NPs consisting of metal cores and Si NC shells are spontaneously formed. We demonstrate the synthesis of highly uniform and size controllable hybrid NPs. It is shown that codoped Si NCs act as a reducing agent for metal salts and also as a protecting layer to stop metal NP growth. The process is thus self-limiting. The development of a variety of Si NC-based hybrid NPs is a promising first step for the design of biocompatible multifunctional NPs with broad material choices for biosensing, bioimaging and solar energy conversion.

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