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1.
Opt Express ; 32(2): 2356-2363, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38297768

RESUMEN

Terahertz scattering-type scanning near-field optical microscopy (THz-sSNOM) provides a noninvasive way to probe the low frequency conductivity of materials and to characterize material compositions at the nanoscale. However, the potential capability of atomic compositional analysis with THz nanoscopy remains largely unexplored. Here, we perform THz near-field imaging and spectroscopy on a model rare-earth alloy of lanthanum silicide (La-Si) which is known to exhibit diverse compositional and structural phases. We identify subwavelength spatial variations in conductivity that is manifested as alloy microstructures down to much less than 1 µm in size and is remarkably distinct from the surface topography of the material. Signal contrasts from the near-field scattering responses enable mapping the local silicon/lanthanum content differences. These observations demonstrate that THz-sSNOM offers a new avenue to investigate the compositional heterogeneity of material phases and their related nanoscale electrical as well as optical properties.

2.
Phys Rev Lett ; 124(15): 157401, 2020 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-32357060

RESUMEN

We discover hidden Rashba fine structure in CH_{3}NH_{3}PbI_{3} and demonstrate its quantum control by vibrational coherence through symmetry-selective vibronic (electron-phonon) coupling. Above a critical threshold of a single-cycle terahertz pump field, a Raman phonon mode distinctly modulates the middle excitonic states with persistent coherence for more than ten times longer than the ones on two sides that predominately couple to infrared phonons. These vibronic quantum beats, together with first-principles modeling of phonon periodically modulated Rashba parameters, identify a threefold excitonic fine structure splitting, i.e., optically forbidden, degenerate dark states in between two bright ones with a narrow, ∼3 nm splitting. Harnessing of vibronic quantum coherence and symmetry inspires light-perovskite quantum control and sub-THz-cycle "Rashba engineering" of spin-split bands for ultimate multifunction device.

3.
Eur J Neurol ; 27(2): 343-351, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31535427

RESUMEN

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.


Asunto(s)
Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Alberta , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Tiempo de Tratamiento , Resultado del Tratamiento
4.
J Chem Phys ; 151(24): 244706, 2019 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-31893879

RESUMEN

We report the discovery of helicity-dependent ultrafast photocurrent generation in organic-inorganic perovskite by measuring terahertz (THz) electric field emissions in the time-domain. We find signatures of the circular photogalvanic effect (CPGE) where right circularly polarized light and left circularly polarized light lead to different photocurrent generation. The direction of photocurrent is also resolved by measuring the polarization of the emitted THz pulses. Furthermore, we observe distinct wavelength-dependent, coherent phonon dynamics using THz pump-induced differential reflectivity, indicative of multiple exciton resonances. Both the CPGE and exciton fine structure, together with theoretical simulations, provide compelling and complementary evidence for the existence of Rashba-type bands in perovskite.

5.
Lett Appl Microbiol ; 66(4): 300-305, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29315769

RESUMEN

Klebsiella oxytoca naturally produces a large amount of 2,3-butanediol (2,3-BD), a promising chemical with wide industrial applications, along with various by-products. Previously, we have developed a metabolically engineered K. oxytoca ΔldhA ΔpflB strain to reduce the formation of by-products. To improve 2,3-BD productivity and examine the stability of K. oxytoca ΔldhA ΔpflB strain for industrial application, a semi-continuous two-stage simultaneous saccharification and fermentation (STSSF) process was developed. The STSSF with the K. oxytoca ΔldhA ΔpflB mutant using cassava as a carbon source could produce 108 ± 3·73 g(2,3-BD)  l-1 with a yield of 0·45 g(2,3-BD)  g(glucose)-1 and a productivity of 3·00 g(2,3-BD) l-1  h-1 . No apparent changes in the final titre, yield and productivity of 2,3-BD were observed for up to 20 cycles of STSSF. Also, microbial contamination and spontaneous mutation of the host strain with potential detrimental effects on fermentation efficiency did not occur during the whole fermentation period. These results strongly underpin that the K. oxytoca ΔldhA ΔpflB mutant is stable and that the STSSF process is commercially exploitable. SIGNIFICANCE AND IMPACT OF THE STUDY: There is growing interest in the production of 2,3-butanediol (2,3-BD) from renewable resources by microbial fermentation because of its wide applications to specialty and commodity chemical industries. Klebsiella oxytoca usually produces 2,3-BD as a major end product during the fermentation of carbohydrates. This is the first study to provide a high-efficiency simultaneous saccharification and 2,3-BD fermentation process. Also, this study proves the stability of a metabolically engineered 2,3-BD overproducing K. oxytoca strain for industrial application.


Asunto(s)
Reactores Biológicos/microbiología , Butileno Glicoles/metabolismo , Klebsiella oxytoca/metabolismo , Ingeniería Metabólica/métodos , Fermentación/genética , Fermentación/fisiología , Glucosa/metabolismo
6.
Clin Otolaryngol ; 43(1): 137-143, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28605121

RESUMEN

OBJECTIVE: To analyse the association between 24-hour multichannel intraluminal impedance-pH (24-h MII-pH) parameters and each item of the reflux finding score (RFS) to determine whether the laryngoscopic findings of the RFS could reflect the characteristics of reflux in patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Prospective cohort study. SETTINGS: Tertiary care referral medical centre. PARTICIPANTS: Patients complaining of LPR symptoms were evaluated via a 24-hour MII-pH. Among them, 99 patients whose LPR was confirmed via 24-hour MII-pH were enrolled in this study. MAIN OUTCOME MEASURES: Correlations between RFS ratings and 24-hour MII-pH parameters were evaluated and compared between patients with or without each laryngoscopic finding used in the RFS. RESULTS: Subglottic oedema had a statistically significant positive correlation with number of non-acid LPR and non-acid full column reflux events. Ventricular obliteration and posterior commissure hypertrophy showed a significant correlation with non-acid exposure time and total reflux exposure time. We also found a significant correlation between granuloma/granulation score and number of acid LPR events. The numbers of non-acid LPR and full column reflux events in patients with subglottic oedema were significantly higher than those without subglottic oedema. CONCLUSION: Among the laryngoscopic findings used in the RFS, subglottic oedema is specific for non-acid reflux episodes, and granuloma/granulation is specific for acid reflux episodes.


Asunto(s)
Reflujo Laringofaríngeo/diagnóstico , Laringoscopía/métodos , Encuestas y Cuestionarios , Monitorización del pH Esofágico , Femenino , Estudios de Seguimiento , Humanos , Reflujo Laringofaríngeo/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo
7.
Nutr Metab Cardiovasc Dis ; 27(5): 456-461, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28428029

RESUMEN

BACKGROUND AND AIMS: Increasing evidence has indicated that insulin resistance is associated with inflammation. However, few studies have investigated the association between white blood cell (WBC) count and insulin resistance, as measured by a homeostasis model assessment of insulin resistance (HOMA-IR) in a general pediatric population. This study aimed to examine the association between WBC count and insulin resistance as measured by HOMA-IR in a nationally representative sample of children and adolescents. METHODS AND RESULTS: In total, 2761 participants (1479 boys and 1282 girls) aged 10-18 years were selected from the 2008-2010 Korean National Health and Nutrition Examination Survey. Insulin resistance was defined as a HOMA-IR value greater than the 90th percentile. The odds ratios and 95% confidence intervals for insulin resistance were determined using multiple logistic regression analysis. The mean values of most cardiometabolic variables tended to increase proportionally with WBC count quartiles. The prevalence of insulin resistance significantly increased in accordance with WBC count quartiles in both boys and girls. Compared to individuals in the lowest WBC count quartile, the odds ratio for insulin resistance for individuals in the highest quartile was 2.84 in boys and 3.20 in girls, after adjusting for age, systolic blood pressure, body mass index, and waist circumference. CONCLUSION: A higher WBC count was positively associated with an increased risk of insulin resistance in Korean children and adolescents. This study suggests that WBC count could facilitate the identification of children and adolescents with insulin resistance.


Asunto(s)
Inflamación/sangre , Resistencia a la Insulina , Recuento de Leucocitos , Síndrome Metabólico/sangre , Adolescente , Factores de Edad , Biomarcadores/sangre , Glucemia/análisis , Niño , Estudios Transversales , Femenino , Humanos , Inflamación/diagnóstico , Inflamación/epidemiología , Insulina/sangre , Modelos Logísticos , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Análisis Multivariante , Encuestas Nutricionales , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prevalencia , República de Corea/epidemiología , Medición de Riesgo , Factores de Riesgo
8.
J Fish Biol ; 91(6): 1582-1602, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29034467

RESUMEN

Potential roles of the rostrum of sawsharks (Pristiophoridae), including predation and self-defence, were assessed through a variety of inferential methods. Comparison of microwear on the surface of the rostral teeth of sawsharks and sawfishes (Pristidae) show that microwear patterns are alike and suggest that the elongate rostra in these two elasmobranch families are used for a similar purpose (predation). Raman spectroscopy indicates that the rostral teeth of both sawsharks and sawfishes are composed of hydroxyapatite, but differ in their collagen content. Sawfishes possess collagen throughout their rostral teeth whereas collagen is present only in the centre of the rostral teeth of sawsharks, which may relate to differences in ecological use. The ratio of rostrum length to total length in the common sawshark Pristiophorus cirratus was found to be similar to the largetooth sawfish Pristis pristis but not the knifetooth sawfish Anoxypristis cuspidata. Analysis of the stomach contents of P. cirratus indicates that the diet consists of demersal fishes and crustaceans, with shrimp from the family Pandalidae being the most important dietary component. No prey item showed evidence of wounds inflicted by the rostral teeth. In light of the similarities in microwear patterns, rostral tooth chemistry and diet with sawfishes, it is hypothesised that sawsharks use their rostrum in a similar manner for predation (sensing and capturing prey) and possibly for self-defence.


Asunto(s)
Elasmobranquios/fisiología , Diente/anatomía & histología , Animales , Dieta , Elasmobranquios/anatomía & histología , Conducta Predatoria , Rajidae , Espectrometría Raman , Diente/química , Diente/fisiología
9.
Clin Otolaryngol ; 42(3): 584-591, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28004504

RESUMEN

OBJECTIVE: To evaluate the association between the parameters of 24-hour multichannel intraluminal impedance (MII)-pH monitoring and the symptoms or quality of life (QoL) in laryngopharyngeal reflux (LPR) patients. DESIGN: Prospective cohort study without controls. SETTING: University teaching hospital. METHODS: Forty-five LPR patients were selected from subjects who underwent 24-hour MII-pH monitoring and were diagnosed with LPR from September 2014 to May 2015. Reflux Symptom Index (RSI), Health-related Quality of Life (HRQoL), Short Form 12 (SF-12) Survey questionnaires were surveyed. Spearman's correlation was used to analyse the association between the symptoms or QoL and 24-hour MII-pH monitoring. RESULTS: Most parameters in 24-hour MII-pH monitoring showed weak or no correlation with RSI, HRQoL and SF-12. Only number of non-acid reflux events that reached the larynx and pharynx (LPR-non-acid) and number of total reflux events that reached the larynx and pharynx (LPR-total) parameters showed strong correlation with heartburn in RSI (R = 0.520, P < 0.001, R = 0.478, P = 0.001, respectively). Multiple regression analysis showed that there was only one significant regression coefficient between LPR-non-acid and voice/hoarseness portion of HRQoL (b = 1.719, P = 0.022). CONCLUSION: Most parameters of 24-hour MII-pH monitoring did not reflect subjective symptoms or QoL in patients with LPR.


Asunto(s)
Monitorización del pH Esofágico/métodos , Reflujo Laringofaríngeo/diagnóstico , Calidad de Vida , Impedancia Eléctrica , Esófago/metabolismo , Esófago/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Reflujo Laringofaríngeo/fisiopatología , Reflujo Laringofaríngeo/psicología , Laringe/metabolismo , Laringe/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
10.
Transpl Infect Dis ; 18(5): 714-720, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27501504

RESUMEN

BACKGROUND: Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. METHODS: In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. RESULTS: The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CONCLUSION: CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment.


Asunto(s)
Antibacterianos/farmacología , Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/tratamiento farmacológico , Inmunosupresores/farmacología , Metronidazol/farmacología , Trasplante de Órganos/efectos adversos , Tacrolimus/farmacología , Vancomicina/farmacología , Adulto , Anciano , Antibacterianos/uso terapéutico , Toma de Decisiones Clínicas , Infecciones por Clostridium/microbiología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Masculino , Metronidazol/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Vancomicina/uso terapéutico
11.
J Appl Microbiol ; 118(4): 881-9, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25597384

RESUMEN

AIMS: To investigate the impact of the highly variable C-terminal domain of cyanide dihydratase, a member of the nitrilase superfamily, on its activity and stability. METHODS AND RESULTS: Generating and analysing the thermal stability and pH tolerance of chimeric cyanide dihydratase proteins has provided a platform to investigate domains within the C-terminus and their effect on quaternary structure of the protein. The protein oligomerization state was inferred from native protein size by gel exclusion chromatography. CONCLUSIONS: Our data indicates that the influence of the cyanide dihydratase C-terminus on thermal stability stems from its participation in oligomerization at the major C-surface interface. The formation of this surface is crucial for the activity and stability of CynD. Gel filtration chromatography of an N-terminal deletion mutant, CynDpum ∆303, revealed a defect in oligomerization, and another mutant R67C was suppressed by introduction of a heterologous C-terminus as a chimeric protein. This indicates that the C-terminus from Pseudomonas stutzeri stabilizes CynD by supporting oligomerization between dimers at the C-surface. The chimeric protein CynDpum-stut exhibited full activity at pH 9, a pH where the parent enzyme is nearly inactive, and retained 40% of its activity at pH 9·5 making it a unique pH tolerant mutant. SIGNIFICANCE AND IMPACT OF THE STUDY: The study characterized a chimeric protein with remarkable thermal stability and tolerance to alkaline conditions, features essential for practical application as industrial cyanide solutions are maintained as highly alkaline solutions to prevent formation of hydrogen cyanide gas.


Asunto(s)
Bacillus/enzimología , Hidrolasas/química , Hidrolasas/genética , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Hidrolasas/metabolismo , Mutación , Multimerización de Proteína , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Temperatura
12.
Asian-Australas J Anim Sci ; 28(2): 180-7, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25557813

RESUMEN

This study was conducted to determine the effects of feeding by-product feed (BF)-based silage on the performance, blood metabolite parameters, and carcass characteristics of Hanwoo steers. The BF-based silage was composed of 50% spent mushroom substrate, 21% recycled poultry bedding, 15% cut ryegrass straw, 10.8% rice bran, 2% molasses, 0.6% bentonite, and 0.6% microbial additive (on a wet basis), and ensiled for over 5 d. Fifteen steers were allocated to three diets during the growing and fattening periods (3.1 and 9.8 months, respectively): a control diet (concentrate mix and free access to rice straw), a 50% BF-based silage diet (control diet+50% of maximum BF-based silage intake), and a 100% BF-based silage diet (the same amount of concentrate mix and ad libitum BF-based silage). The BF-based silage was fed during the growing and fattening periods, and was replaced with larger particles of rice straw during the finishing period. After 19.6 months of the whole period all the steers were slaughtered. Compared with feeding rice straw, feeding BF-based silage tended (p = 0.10) to increase the average daily gain (27%) and feed efficiency (18%) of the growing steers, caused by increased voluntary feed intake. Feeding BF-based silage had little effect on serum constituents, electrolytes, enzymes, or the blood cell profiles of fattening steers, except for low serum Ca and high blood urea concentrations (p<0.05). Feeding BF-based silage did not affect cold carcass weight, yield traits such as back fat thickness, longissimus muscle area, yield index or yield grade, or quality traits such as meat color, fat color, texture, maturity, marbling score, or quality grade. However, it improved good quality grade (1(+) and 1(++)) appearance rates (60% for the control group vs 100% for the BF-based silage-fed groups). In conclusion, cheap BF-based silage could be successfully used as a good quality roughage source for beef cattle.

13.
Water Sci Technol ; 69(8): 1768-74, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24759540

RESUMEN

In this study, a process that combines the mesophilic anaerobic digestion (MAD) process with thermophilic aerobic digestion (TAD) for high-strength food wastewater (FWW) treatment was developed to examine the removal of organic matter and methane production. All effluent discharged from the MAD process was separated into solid and liquid portions. The liquid part was discarded and the sludge part was passed to the TAD process for further degradation. Then, the digested sludge from the TAD process was recycled back to the MAD unit to achieve low sludge discharge from the combined process. The reactor combination was operated in two phases: during Phase I, 40 d of total hydraulic retention time (HRT) was applied; during Phase II, 20 d was applied. HRT of the TAD process was fixed at 5 d. For a comparison, a control process (single-stage MAD) was operated with the same HRTs of the combined process. Our results indicated that the combined process showed over 90% total solids, volatile solids and chemical oxygen demand removal efficiencies. In addition, the combined process showed a significantly higher methane production rate than that of the control process. Consequently, the experimental data demonstrated that the combined MAD-TAD process was successfully employed for high-strength FWW treatment with highly efficient organic matter reduction and methane production.


Asunto(s)
Industria de Alimentos , Residuos Industriales , Aguas del Alcantarillado , Eliminación de Residuos Líquidos/métodos , Aerobiosis , Anaerobiosis , Concentración de Iones de Hidrógeno , Factores de Tiempo
14.
J Phys Condens Matter ; 36(21)2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38354419

RESUMEN

We present a comprehensive investigation of the crystal and magnetic structures of the van der Waals antiferromagnetα-RuCl3using single crystal x-ray and neutron diffraction. The crystal structure at room temperature is a monoclinic (C2/m). However, with decreasing temperature, a remarkable first-order structural phase transition is observed, leading to the emergence of a rhombohedral (R3-) structure characterized by three-fold rotational symmetry forming an isotropic honeycomb lattice. On further cooling, a zigzag-type antiferromagnetic order develops belowTN=6∼6.6K. The critical exponent of the magnetic order parameter was determined to beß=0.11(1), which is close to the two-dimensional Ising model. Additionally, the angular dependence of the magnetic critical field of the zigzag antiferromagnetic order for the polarized ferromagnetic phase reveals a six-fold rotational symmetry within theab-plane. These findingsreflect the symmetry associated with the Ising-like bond-dependent Kitaev spin interactions and underscore the universality of the Kitaev interaction-dominated antiferromagnetic system.

15.
Diabetologia ; 56(3): 635-43, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23269357

RESUMEN

AIMS/HYPOTHESIS: Transcription factor E3 (TFE3) has been shown to increase insulin sensitivity by activating insulin-signalling pathways. However, the role of TFE3 in glucose homeostasis is not fully understood. Here, we explored the possible therapeutic potential of TFE3 for the control of hyperglycaemia using a streptozotocin-induced mouse model of diabetes. METHODS: We achieved overabundance of TFE3 in streptozotocin mice by administering an adenovirus (Ad) or adeno-associated virus serotype 2 (AAV2). We also performed an oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). To explore molecular mechanisms of blood glucose control by TFE3, transcriptional studies on the regulation of genes involved in hepatic glucose metabolism were performed using quantitative real-time PCR and chromatin immunoprecipitation assay. The binding site of TFE3 in the liver Gck gene promoter was identified using deletion and site-specific mutation studies. RESULTS: Overabundance of TFE3 resulted in reduced hyperglycaemia as shown by the OGTT and ITT in streptozotocin-treated mice. We observed that TFE3 can upregulate Gck in a state of insulin deficiency. However, glucose-6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase mRNA levels were decreased by Ad-mediated overexpression of Tcfe3. Biochemical studies revealed that the anti-hyperglycaemic effect of TFE3 is due to the upregulation of Gck. In primary cultured hepatocytes, TFE3 increased expression of Gck mRNA. Conversely, small interfering RNA-mediated knockdown of TFE3 resulted in a decrease in Gck mRNA. CONCLUSIONS/INTERPRETATION: This study demonstrates that TFE3 counteracts hyperglycaemia in streptozotocin-treated mice. This effect could be due to the upregulation of Gck by binding of TFE3 to its cognitive promoter region.


Asunto(s)
Adenoviridae/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Diabetes Mellitus Experimental/terapia , Glucoquinasa/metabolismo , Hiperglucemia/terapia , Hígado/enzimología , Hígado/metabolismo , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Inmunoprecipitación de Cromatina , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/metabolismo , Glucoquinasa/genética , Prueba de Tolerancia a la Glucosa , Células Hep G2 , Humanos , Hiperglucemia/enzimología , Hiperglucemia/metabolismo , Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas/genética , ARN Interferente Pequeño
16.
Ann Oncol ; 24(5): 1225-31, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23230137

RESUMEN

BACKGROUND: To evaluate the prognostic value of preoperative tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA), in breast cancers. PATIENTS AND METHODS: Preoperative CA 15-3 and CEA levels of 1681 patients were measured. The association of both tumor markers levels with clinicopathological parameters and outcomes was investigated by univariate and multivariate analyses. RESULTS: Among 1681 patients, elevated preoperative CA15-3 and CEA levels were identified in 176 and 131 patients, respectively. Higher preoperative CA 15-3 and CEA levels were significantly associated with a larger tumor size, axillary node metastases, and advanced stage. Patients with elevated CA 15-3 and CEA levels showed worse survival, even in stage-matched analysis. Patients with normal levels of both CA15-3 and CEA showed better survival than those with one or both markers levels elevated. In multivariate analysis, elevated preoperative CA 15-3 and CEA levels were independent prognostic factors. The statistical significance of elevated preoperative tumor markers levels on survival was solidified with longer follow-up and larger study population. CONCLUSIONS: Elevated preoperative CA 15-3 and CEA levels are associated with tumor burden and showed independent prognostic significance. Therefore, new treatment strategies are necessary for patients with elevated preoperative CA 15-3 and CEA levels in clinical practice.


Asunto(s)
Neoplasias de la Mama/sangre , Antígeno Carcinoembrionario/sangre , Mucina-1/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Femenino , Humanos , Persona de Mediana Edad , Periodo Preoperatorio , Pronóstico , Resultado del Tratamiento , Adulto Joven
17.
J Urol ; 190(4): 1371-6, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23624208

RESUMEN

PURPOSE: Two-Step Fowler-Stephens orchiopexy for high undescended testes allows for mobilization of the testicle to the scrotal position while preserving perfusion by collateral circulation after gonadal vessel ligation. Although used for decades, the long-term efficacy of this procedure has not been reported. We present our 28-year clinical experience with this technique. MATERIALS AND METHODS: We retrospectively studied a cohort of patients who underwent 2-step Fowler-Stephens orchiopexy at our institution between 1982 and 2009. Patients were excluded if either step was performed elsewhere or if followup was less than 6 months. Bivariate and multivariate analyses were performed to determine associations between clinical, surgical and anatomical factors and testicular viability at last followup. RESULTS: A total of 62 patients (79 testes) met inclusion criteria. Median followup was 3.1 years (range 0.6 to 20). Based on the most recent examination/ultrasound, 70.9% of testicles were considered to be normal, with the remainder exhibiting relative (15.2%) or complete (14.9%) atrophy. Of the 10 testes assessed at or after puberty 6 were normal and 4 showed relative atrophy. On bivariate and multivariate analyses only an open second stage approach was associated with normal testicular viability, with 69.9% of normal vs 18.9% of completely atrophic testes being managed by an open approach (p = 0.0084). CONCLUSIONS: Thought to be highly effective in short-term followup, our data suggest that 2-step Fowler-Stephens orchiopexy leads to complete testicular viability in 70.9% of cases. This viability is strongly associated with an open second step.


Asunto(s)
Criptorquidismo/cirugía , Orquidopexia/métodos , Adolescente , Niño , Preescolar , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de Tiempo
18.
Scand J Immunol ; 78(3): 238-47, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23679814

RESUMEN

Reactive oxygen species (ROS) are produced by dendritic cells (DCs) during antigen presentation in contact hypersensitivity (CHS). ROS cause a number of non-enzymatic protein modifications, such as carbonylation. Carbonylated proteins in DCs in response to hapten have not been fully identified yet. To identify the proteins carbonylated by ROS, murine epidermis-derived DC line XS106 was challenged with a hapten, 2,4,6-trinitrobenzene sulphonic acid (TNBS). MALDI-TOF analysis revealed that heat-shock protein 70 (HSP70) was one of the carbonylated proteins induced by TNBS. To verify the role of HSP70 in TNBS-treated XS106 cell, we fused protein transduction domain (PTD) with HSP70 to facilitate protein delivery into the cell. The transfected fusion protein HSP70 within the cell caused transient increase of the cellular level of HSP70. Transient increase of HSP70 level in XS-106 DCs resulted in inhibition of ROS production, carbonylation of HSP70, p38 MAPK activation and subsequently IL-12 secretion. To investigate the effects of PTD-HSP70 in vivo, ear-swelling experiments with 2,4,6-trinitro-1-chlorobenzene (TNCB) were performed in BALB/c mice. Pretreatment of PTD-HSP70 reduced the CHS response to TNCB in vivo. We report here that carbonylation of HSP70 by ROS is associated with the pathogenesis of CHS, suggesting possibility of HSP70-targeting therapy in CHS.


Asunto(s)
Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Carbonilación Proteica , Especies Reactivas de Oxígeno/metabolismo , Animales , Línea Celular , Dermatitis por Contacto/inmunología , Dermatitis por Contacto/metabolismo , Activación Enzimática , Haptenos/inmunología , Interleucina-12/metabolismo , Ratones , Ratones Endogámicos A , Ratones Endogámicos BALB C , Cloruro de Picrilo/química , Proteínas Recombinantes de Fusión/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Transfección , Ácido Trinitrobencenosulfónico/inmunología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
19.
Eur J Neurol ; 20(5): 824-30, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23294009

RESUMEN

BACKGROUND: Both vertebrobasilar dolichoectasia (VBD) and cerebral microbleeds (CMBs) are related with the risk of intracerebral hemorrhage. We aimed to examine the relationship between the VBD and CMB in ischaemic stroke patients. METHODS: A consecutive series of 182 patients hospitalized because of ischaemic stroke or transient ischaemic attack (TIA), and who underwent gradient echo brain magnetic resonance imaging were retrospectively recruited from a prospective stroke registry. CMB locations were categorized into anterior and posterior circulation. Ectasia was defined as basilar artery (BA) diameter > 4.5 mm, and dolichosis, as either BA bifurcation above the suprasellar cistern or lateral to the margin of the clivus or dorsum sellae. Whether VBD is associated with CMB anywhere in the brain or in anterior or posterior circulation territories was analysed using binary and multinomial logistic regression models. RESULTS: Twenty-four subjects (13.2%) had VBD and 48 (26.4%) had CMBs. CMBs were more frequently observed in patients with VBD than without (66.7% vs. 20.3%, P < 0.001). VBD was significantly associated with CMBs in any location (crude odds ratio, 7.88; 95% confidence interval, 3.10-20.02), in the posterior circulation territory only (9.63; 2.60-34.94), and in both territories (9.25; 3.40-26.29), but not in the anterior circulation only (1.14; 0.009-11.20). These associations remained unchanged after adjusting for age, gender, hypertension, leukoaraiosis and stroke subtype. CONCLUSIONS: VBD in patients with ischaemic stroke or TIA is independently associated with CMBs, especially in the posterior circulation territory.


Asunto(s)
Hemorragia Cerebral/complicaciones , Accidente Cerebrovascular/complicaciones , Insuficiencia Vertebrobasilar/complicaciones , Anciano , Hemorragia Cerebral/patología , Femenino , Humanos , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/patología , Masculino , Persona de Mediana Edad , Neuroimagen , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/patología , Insuficiencia Vertebrobasilar/patología
20.
J Eur Acad Dermatol Venereol ; 27(7): 827-35, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22620682

RESUMEN

BACKGROUND: Complementary and alternative medicine (CAM) is being increasingly used among Koreans with chronic dermatologic diseases, such as androgenetic alopecia (AGA), atopic dermatitis (AD) and psoriasis. OBJECTIVE: To quantify the usage of CAM in Korean patients with AGA, AD or psoriasis, and to offer valid information for the physicians frequently encountering such disorders. METHODS: Outpatients (n = 678) from three tertiary hospitals were investigated independently by constructed and self-directed questionnaire. RESULTS: Of the respondents, 62.1% (421/678) of the subjects reported current or previous use of CAM for their dermatologic conditions (AGA, 67.2%; AD, 68.9%; psoriasis, 46.6%). In AGA, topical applicants (50.2%) were most often used, followed by dietary therapy and health supplements. In AD, bath therapy (39.4%) was most often used, followed by oriental medicine and topical applicants. In psoriasis, oriental medicine (33.9%) was most frequently used, followed by bath therapy and health supplements. The proportion of patients who believed that CAM helped to improve their skin condition was relatively low (AGA, 16.1%; AD, 31.7%; psoriasis, 15.0%). LIMITATIONS: The results may not be applicable to other countries and generalized to general populations. CONCLUSION: These results indicate that CAM is widely used in Korean patients with chronic dermatological diseases despite their dissatisfactions. Thus, the advantages and disadvantages of CAM must be considered before its clinical practice.


Asunto(s)
Alopecia/terapia , Terapias Complementarias/estadística & datos numéricos , Dermatitis Atópica/terapia , Psoriasis/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
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