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1.
Opt Express ; 31(15): 24045-24053, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37475241

RESUMO

Image-based deep learning (IBDL) is an advanced technique for predicting the surface irradiation conditions of laser surface processing technology. In pulsed-laser surface processing techniques, the number of superimposed laser shots is one of the fundamental and essential parameters that should be optimized for each material. Our primary research aims to build an adequate dataset using laser-irradiated surface images and to successfully predict the number of superimposed shots using the pre-trained deep convolutional neural network (CNN) models. First, the laser shot experiments were performed on copper targets using a nanosecond YAG laser with a wavelength of 532 nm. Then, the training data were obtained with the different superimposed shots of 1 to 1024 in powers of 2. After that, we used several pre-trained deep CNN models to predict the number of superimposed laser shots. Based on the dataset with 1936 images, VGG16 shows a high validation accuracy, higher sensitivity, and more than 99% precision than other deep CNN models. Utilizing the VGG16 model with high sensitivity could positively impact the industries' time, efficiency, and overall production.

2.
Adv Exp Med Biol ; 1269: 125-130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33966206

RESUMO

This study aimed to compare cerebral oxyhemoglobin (O2Hb) levels during incremental exercise by cycling vs. arm cranking in 12 healthy adult men aged 20.8 ± 0.2 years old. O2Hb was measured by near-infrared spectroscopy. Regions of interest included the left and right prefrontal cortices (LtPFC and RtPFC, respectively), the left and right premotor cortices (LtPMC and RtPMC, respectively), and the supplementary motor area (SMA) bilaterally. After 4 min of rest, 4 min of warm-up was performed by using ergometer followed by incremental exercise (increasing work rate by 5 W/min for arm cranking and 20 W/min for cycling exercise). All values were averaged every tenth of the participant's exercise time period from beginning of incremental exercise to end point. At the middle exercise intensity (50% exercise time), the averaged O2Hb values obtained at all regions of interest seemed to be higher during arm cranking exercise as compared to cycling; however, there were no significant differences between two types of exercise. At the end point of incremental exercise (100% exercise time), the O2Hb obtained at all regions of interest was significantly higher during arm cranking exercise compared to cycling (LtPFC 0.081 ± 0.019 vs. -0.001 ± 0.013 mM·cm, RtPFC 0.076 ± 0.021 vs. 0.018 ± 0.015 mM·cm, SMA 0.012 ± 0.040 vs. 0.040 ± 0.016 mM·cm; arm cranking vs. cycling; p < 0.05, respectively). We conclude that exercise-induced cerebral oxygenation is greater with arm cranking than with leg cycling.


Assuntos
Braço , Perna (Membro) , Adulto , Exercício Físico , Teste de Esforço , Humanos , Masculino , Consumo de Oxigênio , Oxiemoglobinas/metabolismo , Adulto Jovem
3.
Anaesthesia ; 75(5): 591-598, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31788784

RESUMO

The present study aimed to develop and validate a model for predicting the need for emergency front-of neck airway (eFONA) procedures among trauma patients. This was a multicentre retrospective cohort study using data from the Japan Trauma Data Bank between January 2004 and December 2017. Only adult trauma patients were included. The cohort was divided into development and validation cohorts. A simple scoring system was developed to predict the necessity for emergency front-of neck airway procedures in the development cohort using a logistic regression model. The external validity and diagnostic ability of the scoring system was assessed in the validation cohort. In total, 198,182 out of 294,274 patients were included; emergency front-of-neck airway occurred in 467 patients (0.24%) they were divided into development (n = 100,120 with 0.22% undergoing emergency front-of neck airway) and validation (n = 98,062 with 0.25% undergoing emergency front-of neck airway) cohorts. The 'eFONA' prediction scoring system was developed in the development cohort, with a score of +1 for each of the following: Eye opening (no eye opening in response to any stimuli); Fall from height or motor bike; Oral-maxillofacial injury; Neck tracheal injury; and Airway management by paramedics. In the validation cohort, the C-statistic of the scoring system was 0.820. Setting the cut-off value at one for rule-out, the sensitivity and negative likelihood ratios were 0.86 and 0.22, respectively. Setting the cut-off value at two for rule-in, the specificity and positive likelihood ratios were 0.91 and 6.6, respectively. The present scoring system may assist in predicting the need for emergency front-of neck airway procedures among the general trauma population.


Assuntos
Pescoço/cirurgia , Traqueotomia/métodos , Ferimentos e Lesões/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Manuseio das Vias Aéreas , Estudos de Coortes , Serviços Médicos de Emergência , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Modelos Anatômicos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Traqueotomia/normas , Adulto Jovem
4.
Int Endod J ; 53(5): 636-646, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31910287

RESUMO

AIM: To elucidate the role of HIF1α in pro-inflammatory cytokine mRNA expression from lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs). METHODOLOGY: mRNA expression of interleukin (IL) 1ß and tumour necrosis factor (TNF) α in LPS-stimulated hDPCs was determined by quantitative RT-PCR. Expression of nuclear factor kappa B (NFκB) p65 and phospho-NFκB p65 was analysed by Western blotting. Activation of NFκB signalling was measured by luciferase assay using a reporter vector containing an NFκB response element. Enforced expression of HIF1α was induced by transfection of expression vectors with native or constitutively active forms of HIF1α. Expression of HIF1α protein in hDPCs was evaluated by immunocytochemistry and Western blotting. One-way analysis of variance and the Tukey-Kramer test were performed to determine a significant difference (P < 0.05). RESULTS: mRNA expression of IL1ß and TNFα, protein expression of phospho-NFκB p65 and LPS-induced NFκB signalling activity were promoted in low oxygen conditions (1% O2 ; P < 0.05). These findings were replicated following enforced expression and stabilization of HIF1α in hDPCs. Dimethyloxalylglycine, an inhibitor of prolyl hydroxylase (a HIF1α degrading enzyme), promoted IL1ß and TNFα mRNA expression and NFκB signalling in LPS-stimulated hDPCs (P < 0.05). HIF1α expression was detected in hDPCs cultured in low oxygen conditions (1% O2 ). LPS stimulation further enhanced HIF1α expression in hDPCs, especially within their nuclei. CONCLUSION: HIF1α promoted mRNA expression of IL1ß and TNFα via NFκB signalling in LPS-stimulated hDPCs, suggesting that HIF1α is involved in the progress of inflammation in dental pulp.


Assuntos
Lipopolissacarídeos , Fator de Necrose Tumoral alfa , Células Cultivadas , Polpa Dentária , Humanos , Hipóxia , Interleucina-1beta , NF-kappa B
5.
Int Endod J ; 53(12): 1653-1665, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32767860

RESUMO

AIM: To elucidate mechanisms by which mineral trioxide aggregate (MTA) suppresses pro-inflammatory cytokine mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. METHODOLOGY: Mineral trioxide aggregate extracts were prepared by immersing set ProRoot MTA in culture medium. RAW264.7 cells were cultured in the presence of LPS and MTA extracts. mRNA expression levels of interleukin (IL)-1α, IL-6, early growth response 2 (Egr2), suppressor of cytokine signalling 3 (Socs3) and IL-10 were quantified with reverse transcription-quantitative polymerase chain reaction. Phosphorylation of nuclear factor-kappa B (NF-κB) p65 in RAW264.7 cells was analysed by Western blotting. Intracellular calcium imaging was performed with Fluo-4 AM. The activity of nuclear factor of activated T cells (NFAT) was determined by luciferase assays. Enforced expression and silencing of Egr2 in RAW264.7 cells were carried out using an expression vector and specific RNAi, respectively. In vivo kinetics of Egr2+ cells in MTA-treated rat molar pulp tissues were examined using immunohistochemistry. Data were analysed by one-way analysis of variance, followed by the Tukey-Kramer test (P < 0.05). RESULTS: Exposure to MTA extracts resulted in reduced mRNA expression levels of IL-1α and IL-6, as well as reduced expression of phosphorylated NF-κB, in LPS-stimulated RAW264.7 cells. Exposure to MTA extracts induced Ca2+ influx, which was blocked by NPS2143, an antagonist of calcium-sensing receptor (CaSR); Ca2+ influx then triggered activation of calcineurin/NFAT signalling and enhanced mRNA expression of Egr2. Enforced expression of Egr2 in RAW264.7 cells promoted the expression of both IL-10 and Socs3. In vivo application of MTA onto rat molar pulp tissue resulted in the appearance of Egr2-expressing cells that coexpressed CD163, a typical M2 macrophage marker. CONCLUSIONS: Mineral trioxide aggregate extracts induced downregulation of IL-1α and IL-6 in LPS-stimulated RAW264.7 cells via CaSR-induced activation of calcineurin/NFAT/Egr2 signalling and subsequent upregulation of IL-10 and Socs3.


Assuntos
Calcineurina , Lipopolissacarídeos , Compostos de Alumínio , Animais , Compostos de Cálcio , Citocinas , Combinação de Medicamentos , Lipopolissacarídeos/farmacologia , Macrófagos , NF-kappa B , Óxidos , Ratos , Silicatos
7.
Nature ; 486(7403): 382-5, 2012 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-22722198

RESUMO

Electronic nematicity, a unidirectional self-organized state that breaks the rotational symmetry of the underlying lattice, has been observed in the iron pnictide and copper oxide high-temperature superconductors. Whether nematicity plays an equally important role in these two systems is highly controversial. In iron pnictides, the nematicity has usually been associated with the tetragonal-to-orthorhombic structural transition at temperature T(s). Although recent experiments have provided hints of nematicity, they were performed either in the low-temperature orthorhombic phase or in the tetragonal phase under uniaxial strain, both of which break the 90° rotational C(4) symmetry. Therefore, the question remains open whether the nematicity can exist above T(s) without an external driving force. Here we report magnetic torque measurements of the isovalent-doping system BaFe(2)(As(1-x)P(x))(2), showing that the nematicity develops well above T(s) and, moreover, persists to the non-magnetic superconducting regime, resulting in a phase diagram similar to the pseudogap phase diagram of the copper oxides. By combining these results with synchrotron X-ray measurements, we identify two distinct temperatures-one at T*, signifying a true nematic transition, and the other at T(s) (

8.
Am J Transplant ; 17(5): 1396-1404, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27977885

RESUMO

Ex vivo lung perfusion (EVLP) enables assessment of marginal donor lungs for transplantation. We aimed to discover biomarkers in EVLP perfusate that could predict development of primary graft dysfunction (PGD). From September 2008 to August 2013, 100 clinical EVLPs were performed. Eleven patients developed PGD grade 3 within 72 h after transplant. The non-PGD group consisted of 34 patients without PGD grade 3. Nonbilateral lung transplants or transplant after extracorporeal life support were excluded from analyses. Soluble intercellular adhesion molecule 1 (sICAM-1), soluble VCAM-1 (sVCAM-1), and soluble E selectin (sE-selectin) levels, as markers of endothelial activation, were measured in the perfusate of EVLP by enzyme-linked immunosorbent assay and were correlated with clinical outcome. Levels of sICAM-1 at 1 h and sVCAM-1 at 1 and 4 h were significantly higher in the PGD group compared with the non-PGD group. The sE selectin levels were not statistically different between the study groups. Higher levels of sVCAM-1 at 1 and 4 h were statistically significantly associated with PGD either alone or after adjustment for other PGD risk factors. These adhesion molecules may help identify donor lungs at higher risk of PGD during EVLP.


Assuntos
Biomarcadores/metabolismo , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Disfunção Primária do Enxerto/diagnóstico , Doadores de Tecidos , Adulto , Selectina E/metabolismo , Circulação Extracorpórea , Feminino , Seguimentos , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade , Perfusão , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/metabolismo , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/metabolismo , Prognóstico , Estudos Retrospectivos , Molécula 1 de Adesão de Célula Vascular/metabolismo
9.
Mol Psychiatry ; 21(11): 1504-1510, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26782057

RESUMO

Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, the precise biological basis remains unknown, hampering the search for novel biomarkers. In this study, we performed metabolomics of cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched male healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic analyses, metabolomics of CSF samples from rats treated with lithium or valproic acid were also performed. After multivariate logistic regression, isocitric acid (isocitrate) levels were significantly higher in the CSF from BD patients than healthy controls. Furthermore, gene expression of two subtypes (IDH3A and IDH3B) of isocitrate dehydrogenase (IDH) in the dorsolateral prefrontal cortex from BD patients was significantly lower than that of controls, although the expression of other genes including, aconitase (ACO1, ACO2), IDH1, IDH2 and IDH3G, were not altered. Moreover, protein expression of IDH3A in the cerebellum from BD patients was higher than that of controls. Genetic analyses showed that IDH genes (IDH1, IDH2, IDH3A, IDH3B) and ACO genes (ACO1, ACO2) were not associated with BD. Chronic (4 weeks) treatment with lithium or valproic acid in rats did not alter CSF levels of isocitrate, and mRNA levels of Idh3a, Idh3b, Aco1 and Aco2 genes in the rat brain. These findings suggest that abnormality in the metabolism of isocitrate by IDH3A in the mitochondria plays a key role in the pathogenesis of BD, supporting the mitochondrial dysfunction hypothesis of BD. Therefore, IDH3 in the citric acid cycle could potentially be a novel therapeutic target for BD.


Assuntos
Transtorno Bipolar/metabolismo , Isocitrato Desidrogenase/metabolismo , Adulto , Animais , Transtorno Bipolar/líquido cefalorraquidiano , Encéfalo/metabolismo , Expressão Gênica/genética , Humanos , Isocitrato Desidrogenase/líquido cefalorraquidiano , Isocitratos/metabolismo , Masculino , Metabolômica/métodos , Mitocôndrias/metabolismo , Ratos
10.
Skin Res Technol ; 23(4): 519-524, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28295641

RESUMO

BACKGROUND/PURPOSE: Presently, skin-cleaning agents that claim to be removed by water or wiping alone are commercially available and have been used for the purpose of bed baths. However, there is a lack of knowledge on how water washing and wiping differently affect skin physiological functions or ceramide content. The aim of this study was to compare the effects of water washing and wiping on skin physiological functions and ceramide content. METHODS: Three kinds of the cleaning agents with different removal techniques (ie, water washing and wiping) were used in this study. Skin physiological functions (ie, transepidermal water loss, skin hydration, and skin pH) and skin ceramide content were measured before and after seven consecutive days of the application of each cleaning agent. RESULTS: No significant differences in skin physiological functions or ceramide content were observed between water washing and wiping. CONCLUSION: Cleaning agents that claim to be removed by water washing or wiping do not affect skin physiological functions or ceramide content by either removal method.


Assuntos
Detergentes/farmacologia , Higiene , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Ceramidas/análise , Fármacos Dermatológicos/farmacologia , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Estado de Hidratação do Organismo/efeitos dos fármacos , Pele/química , Higiene da Pele , Água , Perda Insensível de Água/efeitos dos fármacos , Adulto Jovem
11.
Chaos ; 27(10): 104616, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29092416

RESUMO

Irreversible process of a weakly coupled one-dimensional quantum perfect Lorentz gas is studied on the basis of the fundamental laws of physics in terms of the complex spectral analysis associated with the resonance state of the Liouvillian. Without any phenomenological operations, such as a coarse-graining of space-time or a truncation of the higher order correlation, we obtained irreversible processes on a purely dynamical basis in all space and time scale including the microscopic atomic interaction range that is much smaller than the mean-free-length. The list of development of the complex spectral analysis of the Hamiltonian (instead of the Liouvillian) in quantum optical systems and in quantum nano-devices is also presented.

12.
Am J Transplant ; 16(1): 358-63, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26437326

RESUMO

The continual improvement in outcome with highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection and visceral transplantation for gut failure stimulated our interest in lifting HIV infection as a contraindication for intestinal and multivisceral transplantation. This report is the first to describe visceral transplantation in a patient with HIV infection. A HAART regimen was introduced in the setting of short-gut syndrome with successful suppression of HIV viral load. The indication for en bloc multivisceral and kidney transplantation was end-stage liver failure with portomesenteric venous thrombosis and chronic renal insufficiency. The underlying hepatic pathology was alcoholic and home parenteral nutrition-associated cirrhosis. Surgery was complicated due to technical difficulties with excessive blood loss and long operative time. The complex posttransplant course included multiple exploratory laparotomies due to serious intra-abdominal and systemic infections. Heavy immunosuppression was required to treat recurrent episodes of severe allograft rejection. Posttransplant oral HAART successfully sustained undetectable viral load. Unfortunately, the patient succumbed to sepsis 3 months posttransplant. With new insights into the biology of gut immunity, mechanisms of allograft tolerance, and HIV-associated immune dysregulation, successful outcome is anticipated, particularly in patients who are in need of isolated intestinal and less-organ-contained visceral allografts.


Assuntos
Rejeição de Enxerto/diagnóstico , Infecções por HIV/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Falência Hepática/cirurgia , Complicações Pós-Operatórias , Vísceras/transplante , Adulto , Feminino , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , HIV/patogenicidade , Infecções por HIV/virologia , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/etiologia , Falência Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos , Prognóstico , Adulto Jovem
13.
Am J Transplant ; 16(4): 1229-37, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26730551

RESUMO

Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic-treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad-spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL-1ß and macrophage inflammatory proteins 1α and 1ß at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad-spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function.


Assuntos
Anti-Infecciosos/administração & dosagem , Transplante de Pulmão/normas , Pulmão/microbiologia , Perfusão/métodos , Obtenção de Tecidos e Órgãos/normas , Adulto , Anti-Infecciosos/farmacologia , Carga Bacteriana , Líquido da Lavagem Broncoalveolar/microbiologia , Broncopneumonia/tratamento farmacológico , Broncopneumonia/microbiologia , Broncopneumonia/patologia , Estudos de Casos e Controles , Circulação Extracorpórea , Feminino , Seguimentos , Humanos , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doadores de Tecidos
14.
Scand J Rheumatol ; 45(5): 412-22, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26901593

RESUMO

OBJECTIVES: The lectin-like oxidized low density lipoprotein (ox-LDL) receptor 1 (LOX-1)/ox-LDL system, which contributes to the pathogenesis of atherosclerosis, may be involved in the development of osteoarthritis (OA). However, the mechanisms by which the LOX-1/ox-LDL system contributes to OA development in vivo are unclear. In this study, we investigated the direct involvement of LOX-1/ox-LDL in OA development by using LOX-1-knockout (LOX-1(-)/(-)) mice in a joint instability-induced model of OA. METHOD: OA development was evaluated with histological scoring at 4 and 8 weeks after surgery to induce knee destabilization in LOX-1(+)/(+) and LOX-1(-)/(-) mice. Immunohistological analysis was used to evaluate the expression of LOX-1, ox-LDL, Runt-related transcription factor 2 (Runx2), and type X collagen (COL X) in articular chondrocytes and osteophyte-forming cells. In addition, double immunofluorescence staining was performed to determine the relationships between LOX-1 and Runx2 or COL X expression. RESULTS: In the model of knee destabilization, symptoms were significantly suppressed in LOX-1(-)/(-) mice. LOX-1, ox-LDL, Runx2, and COL X were overexpressed in articular chondrocytes and osteophyte-forming cells in LOX-1(+)/(+) mice and were significantly downregulated in articular chondrocytes and osteophyte-forming cells in LOX-1(-)/(-) mice compared with those in LOX-1(+)/(+) mice. Double immunostaining indicated that LOX-1 localization coincided with Runx2 and COL X expression. CONCLUSIONS: These data indicate that the LOX-1/ox-LDL system plays a pivotal role in the pathogenesis of instability-induced OA through endochondral ossification. LOX-1-positive chondrocytes and osteophyte-forming cells may be possible targets to prevent disease progression in OA.


Assuntos
Instabilidade Articular , Osteoartrite do Joelho/genética , Receptores Depuradores Classe E/genética , Animais , Artrite Experimental , Condrócitos/metabolismo , Colágeno Tipo X/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Imuno-Histoquímica , Articulação do Joelho , Lipoproteínas LDL/metabolismo , Masculino , Meniscos Tibiais/cirurgia , Camundongos , Camundongos Knockout , Osteoartrite do Joelho/metabolismo , Osteófito , Receptores Depuradores Classe E/metabolismo , Lesões do Menisco Tibial
15.
Osteoarthritis Cartilage ; 23(11): 1946-54, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26521741

RESUMO

OBJECTIVE: To determine whether altered IL8 methylation status is associated with increased expression of IL8 in human osteoarthritic (OA) chondrocytes. METHODS: IL8 expression levels and the percentage CpG methylation in human chondrocytes were quantified by qRT-PCR and pyrosequencing in OA patients and in non-OA osteoporotic controls. The effect of CpG methylation on IL8 promoter activity was determined using a CpG-free vector; co-transfections with expression vectors encoding nuclear factor-kappa B (NF-κB), AP-1 and C/EBP were subsequently undertaken to analyse for IL8 promoter activity in response to changes in methylation status. RESULTS: IL8 expression in OA patients was 37-fold higher than in osteoporotic controls. Three CpG sites in the IL8 promoter were significantly demethylated in OA patients. Multiple regression analysis revealed that the degree of methylation of the CpG site located at -116-bp was the strongest predictor of IL8 expression. In vitro DNA methylation was noted to decrease IL8 promoter basal activity. Furthermore, NF-κB, AP-1 and C/EBP strongly enhanced IL8 promoter activity whilst DNA methylation inhibited the effects of these three transcription factors. CONCLUSIONS: The present study demonstrates the key role of DNA methylation status on the expression of IL8 in human chondrocytes. We demonstrate a quantitative relationship between percentage methylation and gene expression within clinical samples. These studies provide direct evidence linking the activation of IL8, DNA demethylation and the induction of the OA process with important therapeutic implications therein for patients with this debilitating disease.


Assuntos
Quimiocinas/genética , Condrócitos/metabolismo , DNA/genética , Epigênese Genética/genética , Regulação da Expressão Gênica , Interleucina-8/genética , Osteoartrite/genética , Adulto , Idoso , Células Cultivadas , Quimiocinas/biossíntese , Condrócitos/patologia , Metilação de DNA , Feminino , Humanos , Interleucina-8/biossíntese , Masculino , Pessoa de Meia-Idade , Osteoartrite/metabolismo , Osteoartrite/patologia , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase em Tempo Real
16.
Acta Neurol Scand ; 131(6): 426-30, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25402773

RESUMO

BACKGROUND: The Parkinson's Disease Sleep Scale (PDSS)-2 is a recently developed tool for evaluating disease-related nocturnal disturbances in patients with Parkinson's disease (PD). However, its cutoff score has not been clinically assessed. We determined the optimal cutoff score of the Japanese version of the PDSS-2. METHODS: Patients with PD (n = 146) and controls (n = 100) completed the PDSS-2 and the Pittsburgh Sleep Quality Index (PSQI). Poor sleepers were defined as having global PSQI scores >5. Optimal cutoff scores for determining poor sleepers were assessed using the receiver operating characteristic curve. RESULTS: A PDSS-2 total score ≥ 14 exhibited 82.0% sensitivity and 70.6% specificity, whereas a PDSS-2 total score ≥ 15 provided 72.1% sensitivity and 72.9% specificity in distinguishing poor sleepers (PSQI score >5) from good sleepers (PSQI ≤ 5). Nocturnal disturbances were more frequently observed in patients with PD than in controls (PDSS-2 total score ≥ 14 or ≥ 15; 51.4% vs 20%; 45.9% vs 19%). Nocturnal disturbances were associated with higher Hoehn and Yahr stages and Unified Parkinson's Disease Rating Scale motor scores, impaired quality of life, daytime sleepiness, and depressive symptoms. CONCLUSION: We suggest that PDSS-2 total scores ≥ 15 are useful for detecting poor sleepers among patients with PD.


Assuntos
Doença de Parkinson/complicações , Transtornos do Sono-Vigília/diagnóstico , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/etiologia
17.
J Appl Microbiol ; 119(3): 818-26, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26121394

RESUMO

AIMS: To identify lactic acid bacterial isolates, which promote immunoglobulin A (IgA) production in honeybee products and honeybees (Apis mellifera). METHODS AND RESULTS: Pyrosequencing analysis of the microbiota of honeybee products and honeybees revealed the predominance of Lactobacillus kunkeei in honey, bee pollen, bee bread and royal jelly. Lactobacillus kunkeei was isolated from bee pollen, bee bread and honey stomach, and its effect on IgA production was evaluated in vitro. Heat-killed YB38 and YB83 isolates from bee pollen promoted IgA production in mouse Peyer's Patch cells and had little mitogenic activity or effect on IL-2 production in mouse spleen cells in comparison with Listeria monocytogenes, which does exhibit mitogen activity. A pilot study in 11 healthy adults showed that 4-week intake of 1000 mg day(-1) heat-killed YB38 increased secretory IgA (SIgA) concentrations and secretion in saliva with no adverse effects. CONCLUSION: Heat-killed Lact. kunkeei YB38 from bee pollen increases IgA production and may safely improve immune responsiveness. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of microbiota analysis of royal jelly and the immune efficacy of Lact. kunkeei from honeybee products in humans.


Assuntos
Mel/microbiologia , Imunoglobulina A/imunologia , Lactobacillus/imunologia , Lactobacillus/isolamento & purificação , Adulto , Animais , Abelhas , Feminino , Mel/análise , Humanos , Interleucina-2/imunologia , Lactobacillus/classificação , Lactobacillus/genética , Masculino , Camundongos , Microbiota , Pessoa de Meia-Idade , Dados de Sequência Molecular , Projetos Piloto
18.
Vet Pathol ; 52(3): 566-72, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25248517

RESUMO

Lymphomas are common spontaneous tumors in nonhuman primates but remain poorly characterized in Japanese macaques (Macaca fuscata). This study examined 5 cases of spontaneous malignant lymphoma in Japanese macaques, focusing on the immunophenotypes and presence of simian lymphocryptoviruses, which are Epstein-Barr virus-related herpesviruses in nonhuman primates. The macaques with lymphoma were 5 to 28 years old, indicating that lymphomas develop over a wide age range. The common macroscopic findings were splenomegaly and enlargement of lymph nodes. Histologic and immunohistochemical analyses revealed that all cases were non-Hodgkin type and exhibited a T-cell phenotype, positive for CD3 but negative for CD20 and CD79α. The lymphomas exhibited diverse cellular morphologies and were subdivided into 3 types according to the World Health Organization classification. These included 3 cases of peripheral T-cell lymphoma, not otherwise specified; 1 case of T-cell prolymphocytic leukemia; and 1 case of an unclassifiable T-cell lymphoma. Positive signals were detected by in situ hybridization in 2 of the 4 examined cases using probes for the Epstein-Barr virus-encoded small RNA (EBER). Furthermore, the presence of M. fuscata lymphocryptovirus 2, a macaque homolog of Epstein-Barr virus, was demonstrated in EBER-positive cases by polymerase chain reaction amplification followed by direct sequencing. Immunohistochemistry using antibody to the Epstein-Barr virus-encoded nuclear antigen 2 was negative, even in the EBER-positive cases. The present study suggests that T-cell lymphoma is more common than B-cell lymphoma in Japanese macaques and that M. fuscata lymphocryptovirus 2 is present in some cases.


Assuntos
Linfoma/veterinária , Doenças dos Macacos/patologia , Animais , Feminino , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/veterinária , Hibridização In Situ/veterinária , Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/patologia , Leucemia Prolinfocítica de Células T/veterinária , Leucemia Prolinfocítica de Células T/virologia , Linfonodos/patologia , Lymphocryptovirus , Linfoma/complicações , Linfoma/patologia , Linfoma/virologia , Linfoma de Células T/diagnóstico , Linfoma de Células T/patologia , Linfoma de Células T/veterinária , Linfoma de Células T/virologia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/veterinária , Linfoma de Células T Periférico/virologia , Macaca , Masculino , Doenças dos Macacos/diagnóstico , Doenças dos Macacos/virologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Esplenomegalia/etiologia , Esplenomegalia/patologia , Esplenomegalia/veterinária , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/veterinária , Infecções Tumorais por Vírus/virologia
19.
Am J Transplant ; 14(9): 2072-80, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25040819

RESUMO

Under the "sickest first" Model for End-Stage Liver Disease (MELD) allocation, livers amenable to splitting are most often allocated to patients unsuitable for split liver transplantation (SLT). Our experience with SLT using hemilivers was reviewed. From April 2004 to June 2012, we used 25 lobar grafts (10 left lobes and 15 right lobes) for adult-sized recipients. Twelve recipients were transplanted with primary offers, and 13 were transplanted with leftover grafts. Six grafts were shared with other centers. The data were compared with matched whole liver grafts (n = 121). In 92% of donors, the livers were split in situ. Hemiliver recipients with severe portal hypertension had a greater graft-to-recipient weight ratio than those without severe portal hypertension (1.96% vs. 1.40%, p < 0.05). Hemiliver recipients experienced biliary complications more frequently (32.0% vs. 10.7%, p = 0.01); however, the 5-year graft survival for hemilivers was comparable to whole livers (80.0% vs. 81.5%, p = 0.43). The secondary recipients with leftover grafts did not have increased incidences of graft failure (p = 0.99) or surgical complications (p = 0.43) compared to the primary recipients. In conclusion, while routine application is still controversial due to various challenges, hemiliver SLT can achieve excellent outcomes under the MELD allocation.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/métodos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
20.
Ann Oncol ; 25(10): 1973-1979, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25009009

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) patients are a poor prognostic subgroup, and currently, there is no biomarker for targeted therapy. PATIENTS AND METHODS: Tissue samples were obtained from 75 TNBC patients with lymph-node metastases who had received adjuvant chemotherapy. We examined 11 biomarkers, including PIK3CA and AKT1mutation, with regard to event-free survival (EFS) and overall survival (OS) of patients. RESULTS: In the tumor tissues, phospho-AKT (pAKT) expression was significantly related to HER4 expression. Expression of each of these biomarkers was significantly related to longer EFS (P = 0.024 and 0.03, respectively). pERK expression was also a good prognostic factor regarding EFS and OS in TNBC (P = 0.002 and 0.006, respectively). We also identified a correlation between epidermal growth factor receptor positivity and insulin-like growth factor receptor type 1 positivity (P = 0.001). pERK and T-stage (1-3 versus >3) were independent good prognostic factors by multivariate analysis. CONCLUSIONS: We determined that tumors expressing pAKT or pERK are a good prognostic subtype in node-positive TNBC. Different targeted therapies may be necessary for TNBC that involves activation of PI3K/AKT or MAPK pathways.


Assuntos
Fosfatidilinositol 3-Quinases/biossíntese , Prognóstico , Proteínas Proto-Oncogênicas c-akt/biossíntese , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Classe I de Fosfatidilinositol 3-Quinases , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptor ErbB-2/genética , Receptor ErbB-4/biossíntese , Neoplasias de Mama Triplo Negativas/patologia
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