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1.
Phys Rev Lett ; 133(15): 156506, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39454178

RESUMEN

The observation of time-reversal symmetry breaking and large residual density of states in tetragonal FeSe_{1-x}S_{x} suggests a novel type of ultranodal superconducting state with Bogoliubov Fermi surfaces (BFSs). Although such BFSs in centrosymmetric superconductors are expected to be topologically protected, the impurity effect of this exotic superconducting state remains elusive experimentally. Here, we investigate the impact of controlled defects introduced by electron irradiation on the superconducting state of tetragonal FeSe_{1-x}S_{x} (0.18≤x≤0.25). The temperature dependence of magnetic penetration depth is initially consistent with a model with BFSs in the pristine sample. After irradiation, we observe a nonmonotonic evolution of low-energy excitations with impurity concentrations. This nonmonotonic change indicates a transition from nodal to nodeless, culminating in gapless with Andreev bound states, reminiscent of the nodal s_{±} case. This points to the accidental nature of the possible BFSs in tetragonal FeSe_{1-x}S_{x}, which are susceptible to disruption by the disorder.

2.
Opt Express ; 31(15): 24045-24053, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37475241

RESUMEN

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.

3.
Adv Exp Med Biol ; 1269: 125-130, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33966206

RESUMEN

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.


Asunto(s)
Brazo , Pierna , Adulto , Ejercicio Físico , Prueba de Esfuerzo , Humanos , Masculino , Consumo de Oxígeno , Oxihemoglobinas/metabolismo , Adulto Joven
4.
Anaesthesia ; 75(5): 591-598, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31788784

RESUMEN

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.


Asunto(s)
Cuello/cirugía , Traqueotomía/métodos , Heridas y Lesiones/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Manejo de la Vía Aérea , Estudios de Cohortes , Servicios Médicos de Urgencia , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Modelos Anatómicos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Traqueotomía/normas , Adulto Joven
5.
Int Endod J ; 53(5): 636-646, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31910287

RESUMEN

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.


Asunto(s)
Lipopolisacáridos , Factor de Necrosis Tumoral alfa , Células Cultivadas , Pulpa Dental , Humanos , Hipoxia , Interleucina-1beta , FN-kappa B
6.
Int Endod J ; 53(12): 1653-1665, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32767860

RESUMEN

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.


Asunto(s)
Calcineurina , Lipopolisacáridos , Compuestos de Aluminio , Animales , Compuestos de Calcio , Citocinas , Combinación de Medicamentos , Lipopolisacáridos/farmacología , Macrófagos , FN-kappa B , Óxidos , Ratas , Silicatos
9.
Nature ; 486(7403): 382-5, 2012 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-22722198

RESUMEN

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) (

10.
Am J Transplant ; 17(5): 1396-1404, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27977885

RESUMEN

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.


Asunto(s)
Biomarcadores/metabolismo , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Disfunción Primaria del Injerto/diagnóstico , Donantes de Tejidos , Adulto , Selectina E/metabolismo , Circulación Extracorporea , Femenino , Estudios de Seguimiento , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Masculino , Persona de Mediana Edad , Perfusión , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/metabolismo , Disfunción Primaria del Injerto/etiología , Disfunción Primaria del Injerto/metabolismo , Pronóstico , Estudios Retrospectivos , Molécula 1 de Adhesión Celular Vascular/metabolismo
11.
Mol Psychiatry ; 21(11): 1504-1510, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-26782057

RESUMEN

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.


Asunto(s)
Trastorno Bipolar/metabolismo , Isocitrato Deshidrogenasa/metabolismo , Adulto , Animales , Trastorno Bipolar/líquido cefalorraquídeo , Encéfalo/metabolismo , Expresión Génica/genética , Humanos , Isocitrato Deshidrogenasa/líquido cefalorraquídeo , Isocitratos/metabolismo , Masculino , Metabolómica/métodos , Mitocondrias/metabolismo , Ratas
12.
Skin Res Technol ; 23(4): 519-524, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28295641

RESUMEN

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.


Asunto(s)
Detergentes/farmacología , Higiene , Fenómenos Fisiológicos de la Piel/efectos de los fármacos , Ceramidas/análisis , Fármacos Dermatológicos/farmacología , Voluntarios Sanos , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacos , Estado de Hidratación del Organismo/efectos de los fármacos , Piel/química , Cuidados de la Piel , Agua , Pérdida Insensible de Agua/efectos de los fármacos , Adulto Joven
13.
Chaos ; 27(10): 104616, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29092416

RESUMEN

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.

14.
Am J Transplant ; 16(1): 358-63, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26437326

RESUMEN

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.


Asunto(s)
Rechazo de Injerto/diagnóstico , Infecciones por VIH/complicaciones , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Fallo Hepático/cirugía , Complicaciones Posoperatorias , Vísceras/trasplante , Adulto , Femenino , Rechazo de Injerto/etiología , Supervivencia de Injerto , VIH/patogenicidad , Infecciones por VIH/virología , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/etiología , Fallo Hepático/etiología , Masculino , Persona de Mediana Edad , Trasplante de Órganos , Pronóstico , Adulto Joven
15.
Am J Transplant ; 16(4): 1229-37, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26730551

RESUMEN

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.


Asunto(s)
Antiinfecciosos/administración & dosificación , Trasplante de Pulmón/normas , Pulmón/microbiología , Perfusión/métodos , Obtención de Tejidos y Órganos/normas , Adulto , Antiinfecciosos/farmacología , Carga Bacteriana , Líquido del Lavado Bronquioalveolar/microbiología , Bronconeumonía/tratamiento farmacológico , Bronconeumonía/microbiología , Bronconeumonía/patología , Estudios de Casos y Controles , Circulación Extracorporea , Femenino , Estudios de Seguimiento , Humanos , Pulmón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Pronóstico , Donantes de Tejidos
16.
Scand J Rheumatol ; 45(5): 412-22, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26901593

RESUMEN

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.


Asunto(s)
Inestabilidad de la Articulación , Osteoartritis de la Rodilla/genética , Receptores Depuradores de Clase E/genética , Animales , Artritis Experimental , Condrocitos/metabolismo , Colágeno Tipo X/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Inmunohistoquímica , Articulación de la Rodilla , Lipoproteínas LDL/metabolismo , Masculino , Meniscos Tibiales/cirugía , Ratones , Ratones Noqueados , Osteoartritis de la Rodilla/metabolismo , Osteofito , Receptores Depuradores de Clase E/metabolismo , Lesiones de Menisco Tibial
17.
Osteoarthritis Cartilage ; 23(11): 1946-54, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26521741

RESUMEN

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.


Asunto(s)
Quimiocinas/genética , Condrocitos/metabolismo , ADN/genética , Epigénesis Genética/genética , Regulación de la Expresión Génica , Interleucina-8/genética , Osteoartritis/genética , Adulto , Anciano , Células Cultivadas , Quimiocinas/biosíntesis , Condrocitos/patología , Metilación de ADN , Femenino , Humanos , Interleucina-8/biosíntesis , Masculino , Persona de Mediana Edad , Osteoartritis/metabolismo , Osteoartritis/patología , Regiones Promotoras Genéticas , Reacción en Cadena en Tiempo Real de la Polimerasa
18.
Acta Neurol Scand ; 131(6): 426-30, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25402773

RESUMEN

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.


Asunto(s)
Enfermedad de Parkinson/complicaciones , Trastornos del Sueño-Vigilia/diagnóstico , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Trastornos del Sueño-Vigilia/etiología
19.
J Appl Microbiol ; 119(3): 818-26, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26121394

RESUMEN

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.


Asunto(s)
Miel/microbiología , Inmunoglobulina A/inmunología , Lactobacillus/inmunología , Lactobacillus/aislamiento & purificación , Adulto , Animales , Abejas , Femenino , Miel/análisis , Humanos , Interleucina-2/inmunología , Lactobacillus/clasificación , Lactobacillus/genética , Masculino , Ratones , Microbiota , Persona de Mediana Edad , Datos de Secuencia Molecular , Proyectos Piloto
20.
Vet Pathol ; 52(3): 566-72, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25248517

RESUMEN

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.


Asunto(s)
Linfoma/veterinaria , Enfermedades de los Monos/patología , Animales , Femenino , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/patología , Infecciones por Herpesviridae/veterinaria , Hibridación in Situ/veterinaria , Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/patología , Leucemia Prolinfocítica de Células T/veterinaria , Leucemia Prolinfocítica de Células T/virología , Ganglios Linfáticos/patología , Lymphocryptovirus , Linfoma/complicaciones , Linfoma/patología , Linfoma/virología , Linfoma de Células T/diagnóstico , Linfoma de Células T/patología , Linfoma de Células T/veterinaria , Linfoma de Células T/virología , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/patología , Linfoma de Células T Periférico/veterinaria , Linfoma de Células T Periférico/virología , Macaca , Masculino , Enfermedades de los Monos/diagnóstico , Enfermedades de los Monos/virología , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Esplenomegalia/etiología , Esplenomegalia/patología , Esplenomegalia/veterinaria , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/patología , Infecciones Tumorales por Virus/veterinaria , Infecciones Tumorales por Virus/virología
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