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1.
Sensors (Basel) ; 22(22)2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36433525

RESUMEN

Demonstration of the Salmonella Typhimurium detection system was shown utilizing a quartz crystal microbalance (QCM) biosensor and signal enhancement by gold nanoparticles. In this study, a benchtop system of a QCM biosensor was utilized for the detection of Salmonella Typhimurium. It was designed with a peristaltic pump system to achieve immobilization of antibodies, detection of Salmonella, and the addition of gold nanoparticles to the sensor. As a series of biochemical solutions were introduced to the surface, the proposed system was able to track the changes in the resonant frequency which were proportional to the variations of mass on the sensor. For antibody immobilization, polyclonal antibodies were immobilized via self-assembled monolayers to detect Salmonella O-antigen. Subsequently, Salmonella Typhimurium was detected by antibodies and the average frequency before and after detecting Salmonella was compared. The highest frequency shifts were −26.91 Hz for 109 CFU/mL while the smallest frequency shift was −3.65 Hz corresponding to 103 CFU/mL. For the specificity tests, non-Salmonella samples such as E. coli, Listeria, and Staphylococcus resulted in low cross-reactivity. For signal amplification, biotinylated antibodies reacted to Salmonella followed by streptavidin­100 nm AuNPs through biotin-avidin interaction. The frequency shifts of 103 CFU/mL showed −28.04 Hz, and consequently improved the limit of detection.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Tecnicas de Microbalanza del Cristal de Cuarzo/métodos , Oro/química , Salmonella typhimurium , Escherichia coli , Nanopartículas del Metal/química , Técnicas Biosensibles/métodos
2.
Appl Opt ; 59(3): 801-810, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-32225212

RESUMEN

The silicon photomultiplier (SiPM) for low light detection has many advantages when compared to existing photon counting detectors, such as high sensitivity, low cost, robustness, and compact hardware. To facilitate the use of SiPM as a portable, field deployable device, an electrical circuit was designed consisting of an amplifier, comparator, and microcontroller. In addition, a 3D printing was used to create a portable cradle for housing the SiPM. To evaluate its detection ability, a laser experiment and bioluminescent experiments, including Pseudomonas fluorescens M3A detection, E. coli O157:H7 PhiV10nluc lysogen detection, and a luminescence-based detection of E. coli O157:H7 in ground meat using the engineered luminescent-based reporter phage PhiV10nluc, were conducted. In the same experimental setting, our previously developed smartphone-based luminometer called the bioluminescent-based analyte quantitation by smartphone and a conventional photomultiplier tube-based benchtop luminometer were used to compare detection levels and applicability for supporting luminescent phage-based pathogen detection. Results showed that the SiPM provides better performance in terms of time to detection and SNR and could be used as the light detection component of the PhiV10nluc phage-based detection format.


Asunto(s)
Técnicas Biosensibles/instrumentación , Escherichia coli O157/aislamiento & purificación , Mediciones Luminiscentes/instrumentación , Pseudomonas fluorescens/aislamiento & purificación , Carne Roja/microbiología , Animales , Técnicas Biosensibles/métodos , Calibración , Bovinos , Diseño de Equipo , Escherichia coli O157/metabolismo , Contaminación de Alimentos , Microbiología de Alimentos , Rayos Láser , Luz , Luminiscencia , Mediciones Luminiscentes/métodos , Fotones , Impresión Tridimensional , Pseudomonas fluorescens/metabolismo , Relación Señal-Ruido , Silicio , Teléfono Inteligente
3.
World J Surg Oncol ; 12: 200, 2014 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-25000948

RESUMEN

BACKGROUND: The relationship between the number of parathyroid glands preserved and hypoparathyroidism is not well understood. We sought to determine the number of parathyroid glands that need to be preserved to prevent hypoparathyroidism. METHODS: We analyzed 454 patients who underwent total thyroidectomy for papillary thyroid carcinoma. We analyzed the frequency of hypoparathyroidism according to the number of parathyroid glands preserved. RESULTS: Incidental parathyroidectomy occurred in 19.8% of the patients; one parathyroid gland in 17.6%, two in 1.5%, and three in 0.7%. Transient hypoparathyroidism was increased when incidental parathyroidectomy occurred (odds ratio 1.83, 95% confidence interval 1.04 to 3.23, P = 0.036) on multivariate regression analysis, but was not influenced by the actual number of parathyroid glands removed. There was no relationship between the number of parathyroid glands preserved and permanent hypoparathyroidism (P = 0.147). CONCLUSIONS: Preservation of all parathyroid glands decreases transient hypoparathyroidism compared with when three or fewer glands are preserved, but does not affect permanent hypoparathyroidism. During total thyroidectomy, preserving at least one parathyroid gland with an intact blood supply appears to be sufficient to prevent permanent hypoparathyroidism when autotransplantation is not performed.


Asunto(s)
Carcinoma Papilar/cirugía , Hipoparatiroidismo/fisiopatología , Tratamientos Conservadores del Órgano , Glándulas Paratiroides/fisiopatología , Paratiroidectomía , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Papilar/patología , Femenino , Estudios de Seguimiento , Humanos , Hipoparatiroidismo/etiología , Hipoparatiroidismo/prevención & control , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias de la Tiroides/patología , Adulto Joven
4.
Surg Radiol Anat ; 36(5): 439-45, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24071778

RESUMEN

PURPOSE: To evaluate the clinical and radiological features and the risk of middle ear disease in the contralateral ears of unilateral cholesteatoma with clinical and radiological assessment. METHODS: Fifty-two patients with unilateral cholesteatoma and 30 control subjects underwent otoscopic and audiologic examination. Temporal bone computed tomography was performed to evaluate the pneumatization of the temporal bones, the status of anterior epitympanic space and eustachian tube. Then, the parameters of the temporal bone pneumatization were calculated. RESULTS: 28% of the contralateral ears in the cholesteatoma patients showed abnormal tympanic membrane findings. In the audiologic examination, 10% of the contralateral ears showed moderate hearing loss and 3% showed severe hearing loss. Aeration areas were 1.81 ± 1.01, 2.50 ± 1.31 and 4.49 ± 1.45 cm(2), aeration ratios were 24, 28 and 42%, in cholesteatoma, contralateral and control ears, respectively. Development of the anterior epitympanic space and eustachian tube patency was reduced in contralateral ears relative to control ears. CONCLUSIONS: The degree of temporal bone pneumatization, eustachian tube function, and development of the anterior epitympanic space are significantly decreased in the contralateral ears of unilateral cholesteatoma patients, and there is an increased risk of middle ear diseases. Continuous monitoring of the contralateral ear is crucial for early detection and optimal treatment of middle ear disease.


Asunto(s)
Colesteatoma del Oído Medio/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Trompa Auditiva/diagnóstico por imagen , Femenino , Pruebas Auditivas , Humanos , Masculino , Apófisis Mastoides/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Tomografía Computarizada por Rayos X , Adulto Joven
5.
Curr Res Food Sci ; 8: 100726, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590692

RESUMEN

This study reported an application of Au nanogap substrates for surface-enhanced Raman scattering (SERS) measurements to quantitatively analyze melamine and its derivative products at trace levels in pet liquid food (milk) combined with a waveband selection approach, namely variable importance in projection (VIP). Six different concentrations of melamine, cyanuric acid, and melamine combined with cyanuric acid were created, and SERS spectra were acquired from 550 to 1620cm-1. Detection was possible up to 200 pM for melamine-contaminated samples, and 400 pM concentration detection for other two groups. The VIP-PLSR models obtained correlation coefficient (R2) values of 0.997, 0.985, and 0.981, with root mean square error of prediction (RMSEP) values of 18.492 pM, 19.777 pM, and 15.124 pM for prediction datasets. Additionally, partial least square discriminant analysis (PLS-DA) was used to classify both pure and different concentrations of spiked samples. The results showed that the maximum classification accuracy for melamine was 100%, for cyanuric acid it was 96%, and for melamine coupled with cyanuric acid it was 95%. The results obtained clearly demonstrated that the Au nanogap substrate offers low-concentration, rapid, and efficient detection of hazardous additive chemicals in pet consuming liquid food.

6.
Eur J Immunol ; 41(5): 1266-77, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21469085

RESUMEN

Traumatic spinal cord injury (SCI) is followed by massive infiltration and activation of myeloid cells such as neutrophils and macrophages, but the functions of these cells are controversial. In this study, our objective was to elucidate the in vivo role of a signaling pathway involved in activation of these innate immune cells in SCI using myeloid cell-specific IκB kinase (IKK)-ß conditional knockout (ikkßΔmye) mice. In these mice, the ikkß gene has been specifically deleted from myeloid cells, compromising their in vivo IKK/NF-κB-dependent activation. We found that ikkßΔmye mice had significantly reduced neutrophil and macrophage infiltrations after SCI compared to ikkß(+/+) controls. SCI-induced proinflammatory gene expression was also reduced in ikkßΔmye mice. Reduced neuroinflammation in ikkßΔmye mice was accompanied by attenuated neuronal loss and behavioral deficits in motor activity. In addition, the SCI-induced expression of CXC ligand 1 was reduced in ikkßΔmye mice, which may be responsible for the reduced neutrophil infiltration in these mice. Our data demonstrate that IKK-ß-dependent myeloid cell activation potentiates neuroinflammation and neuronal damage after SCI.


Asunto(s)
Quinasa I-kappa B/metabolismo , Activación de Macrófagos , Macrófagos/inmunología , Neutrófilos/inmunología , Traumatismos de la Médula Espinal/inmunología , Animales , Apoptosis , Muerte Celular , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Expresión Génica , Regulación de la Expresión Génica , Quinasa I-kappa B/genética , Etiquetado Corte-Fin in Situ , Inflamación/genética , Inflamación/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/inmunología , FN-kappa B/metabolismo , Neuronas/patología , Infiltración Neutrófila , Neutrófilos/metabolismo , Reacción en Cadena de la Polimerasa , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Médula Espinal , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología
7.
J Biol Chem ; 285(50): 39447-57, 2010 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-20923777

RESUMEN

Recent studies indicate that Toll-like receptors (TLRs), originally identified as infectious agent receptors, also mediate sterile inflammatory responses during tissue damage. In this study, we investigated the role of TLR2 in excitotoxic hippocampal cell death using TLR2 knock-out (KO) mice. TLR2 expression was up-regulated in microglia in the ipsilateral hippocampus of kainic acid (KA)-injected mice. KA-mediated hippocampal cell death was significantly reduced in TLR2 KO mice compared with wild-type (WT) mice. Similarly, KA-induced glial activation and proinflammatory gene expression in the hippocampus were compromised in TLR2 KO mice. In addition, neurons in organotypic hippocampal slice cultures (OHSCs) from TLR2 KO mouse brains were less susceptible to KA excitotoxicity than WT OHSCs. This protection is partly attributed to decreased expression of proinflammatory genes, such as TNF-α and IL-1ß in TLR2 KO mice OHSCs. These data demonstrate conclusively that TLR2 signaling in microglia contributes to KA-mediated innate immune responses and hippocampal excitotoxicity.


Asunto(s)
Hipocampo/metabolismo , Ácido Kaínico/química , Microglía/metabolismo , Neuronas/metabolismo , Receptor Toll-Like 2/metabolismo , Animales , Muerte Celular , Citocinas/metabolismo , Etiquetado Corte-Fin in Situ , Interleucina-1beta/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor de Necrosis Tumoral alfa/metabolismo
8.
Biol Blood Marrow Transplant ; 17(6): 810-20, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21220034

RESUMEN

Interleukin-6 (IL-6) is a potent pleiotropic cytokine that regulates plasma cell (PC) growth via the IL-6 receptor (IL-6R). We hypothesized that up-regulation of IL-6R in myeloma cells might confer the growth privilege to myeloma cells over bone marrow (BM) hematopoietic cells. We investigated the frequency and prognostic implication of increased copy number of the IL-6R gene by fluorescence in situ hybridization (FISH) in patients with newly diagnosed multiple myeloma (MM). One hundred two patients with newly diagnosed MM were enrolled. The FISH study for IL-6R was performed using a homemade bacterial artificial chromosome (BAC) probe for IL6R at chromosome 1q21. FISH signals were counted among BM plasma cells sorted by cytoplasmic immunoglobulin light chain staining (cIg FISH). The amplification of IL-6R was detected in 53/102 patients (52.0%). The 5-year overall survival (OS) rate of patients with IL-6R gene amplification was 41.3% versus 44.8% for those with a normal IL-6R (P = .425). In 44 patients treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT), patients with ≥3.1 copy numbers of IL-6R per PC showed adverse 5-year OS compared to those with <2.1 copies of IL-6R gene (44.4% versus 78.0%, P = .024). In multivariate analysis, the increase of IL-6R copy numbers (mean copy/PC ≥3.1) could be considered as an independent prognostic factor for MM patients who underwent ASCT. The gain of the IL-6R gene was frequent in myeloma, showing an association with adverse prognosis in myeloma patients treated with ASCT. These findings suggest the potential role of IL-6R in myeloma cell growth and therapeutic implications of the IL-6R blocker in the future.


Asunto(s)
Dosificación de Gen , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Células Plasmáticas/metabolismo , Receptores de Interleucina-6 , Anciano , Antineoplásicos/administración & dosificación , Biomarcadores/análisis , Cromosomas Humanos Par 1/genética , Femenino , Humanos , Cadenas Ligeras de Inmunoglobulina/análisis , Hibridación Fluorescente in Situ , Interleucina-6/metabolismo , Masculino , Mieloma Múltiple/patología , Análisis Multivariante , Células Plasmáticas/patología , Pronóstico , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/metabolismo , Tasa de Supervivencia , Trasplante Autólogo
9.
Ann Hematol ; 90(1): 73-9, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20721556

RESUMEN

Disruption of cell cycle control genes, including p16, is known to contribute to the cancerogenesis of multiple myeloma (MM). We investigated the methylation status of p16 and its association with common cytogenetic changes, clinicolaboratory findings, and survival in MM. Methylation-specific polymerase chain reaction was performed in 99 newly diagnosed MM patients using two different sets of primers (p16M1 and p16M2). Four patterns of p16 promoter methylation were observed: (1) concurrent methylation of p16M1 and p16M2 (P1P2), 27.3%; (2) methylation of p16M1 alone (P1N2), 7.1%; (3) methylation of p16M2 alone (N1P2), 26.3%; and (4) no methylation (N1N2), 39.4%. Patients with p16P1P1 showed shorter survivals than those with the other methylation patterns (P1N2, N1P2, or N1N2; median survival, 12 vs. 43 months; P < 0.001), regardless of the treatment protocol. In a multivariate analysis, p16P1P2 was an independent prognostic factor of adverse outcome in MM. According to International Staging System (ISS), the study population could be divided into 21.2% (20/94) for stage I, 22.3% (21/94) for stage II, and 56.4% (53/94) for stage III (P = 0.003). ISS can divide patients into prognostic groups. Of note, in patients older than 60 years, ISS was not reflective of disease stage (P = 0.114). If p16P1P2 sets up as stage 4 of ISS, modified ISS could be a more reliable staging system irrespective of age in Korean MM patients (P = 0.003 and P = 0.004 in patients younger than 60 years and in patients older than 60 years, respectively). Our study suggests the potential use of p16 methylation status in predicting the outcome of MM patients and the applicability of demethylating agents in MM.


Asunto(s)
Metilación de ADN , Cartilla de ADN/farmacología , Genes p16 , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Reacción en Cadena de la Polimerasa/métodos , Adulto , Anciano , Anciano de 80 o más Años , Metilación de ADN/fisiología , Análisis Mutacional de ADN/métodos , Cartilla de ADN/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Pronóstico , Regiones Promotoras Genéticas/genética , Especificidad por Sustrato , Análisis de Supervivencia
10.
J Korean Med Sci ; 26(8): 991-5, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21860547

RESUMEN

Polymorphisms of DNA repair genes, X-ray repair cross-complementing group 1 (XRCC1) might contribute to individual susceptibility to different types of cancers. We analyzed the relationship between XRCC1 polymorphisms and the risk of papillary thyroid carcinoma in a Korean sample. A hospital-based case-control study was performed in 111 papillary thyroid carcinoma patients and 100 normal control subjects. XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The XRCC1 Arg194Trp Arg/Trp genotype was significantly associated with a decreased risk of papillary thyroid carcinoma compared to that of Arg/Arg genotype (odds ratio [95% confidence intervals]; 0.550 [0.308-0.983]). There was no significant association between XRCC1 Arg399Gln genotypes and risk of papillary thyroid carcinoma. Based on these results, the XRCC1 Arg194Trp Arg/Trp genotype could be used as a useful molecular biomarker to predict genetic susceptibility for papillary thyroid carcinoma in Koreans.


Asunto(s)
Pueblo Asiatico/genética , Proteínas de Unión al ADN/genética , Neoplasias de la Tiroides/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Carcinoma , Carcinoma Papilar , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , República de Corea , Factores de Riesgo , Cáncer Papilar Tiroideo , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X
11.
Am J Otolaryngol ; 32(3): 256-8, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-20444523

RESUMEN

With the emphasis on bilateral hearing nowadays, bilateral cochlear implantation has been tried out for bilateral aural rehabilitation. Bilateral sensorineural hearing loss caused by head trauma can get help from cochlear implantation. We present the case of a 44-year-old man with bilateral otic capsule violating temporal bone fractures due to head trauma. The patient demonstrated much improved audiometric and psychoacoustic performance after bilateral cochlear implantation. We believe bilateral cochlear implantation in such patient can be a very effective tool for rehabilitation.


Asunto(s)
Implantación Coclear/métodos , Pérdida Auditiva Bilateral/cirugía , Pérdida Auditiva Sensorineural/cirugía , Fracturas Craneales/diagnóstico por imagen , Hueso Temporal/lesiones , Adulto , Traumatismos Craneocerebrales/complicaciones , Traumatismos Craneocerebrales/diagnóstico , Estudios de Seguimiento , Pérdida Auditiva Bilateral/diagnóstico , Pérdida Auditiva Bilateral/etiología , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Radiografía , Medición de Riesgo , Fracturas Craneales/complicaciones , Fracturas Craneales/cirugía , Hueso Temporal/cirugía , Resultado del Tratamiento
12.
J Microbiol Methods ; 188: 106288, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34280431

RESUMEN

Salmonella spp. are a foodborne pathogen frequently found in raw meat, egg products, and milk. Salmonella is responsible for numerous outbreaks, becoming a frequent major public-health concern. Many studies have recently reported handheld and rapid devices for microbial detection. This study explored a smartphone-based lateral-flow assay analyzer which employed machine-learning algorithms to detect various concentrations of Salmonella spp. from the test line images. When cell numbers are low, a faint test line is difficult to detect, leading to misleading results. Hence, this study focused on the development of a smartphone-based lateral-flow assay (SLFA) to distinguish ambiguous concentrations of test line with higher confidence. A smartphone cradle was designed with an angled slot to maximize the intensity, and the optimal direction of the optimal incident light was found. Furthermore, the combination of color spaces and the machine-learning algorithms were applied to the SLFA for classifications. It was found that the combination of L*a*b and RGB color space with SVM and KNN classifiers achieved the high accuracy (95.56%). A blind test was conducted to evaluate the performance of devices; the results by machine-learning techniques reported less error than visual inspection. The smartphone-based lateral-flow assay provided accurate interpretation with a detection limit of 5 × 104 CFU/mL commercially available lateral-flow assays.


Asunto(s)
Técnicas Bacteriológicas/métodos , Diagnóstico por Imagen/métodos , Aprendizaje Automático , Salmonella/aislamiento & purificación , Teléfono Inteligente , Animales , Técnicas Biosensibles/instrumentación , Colorimetría/instrumentación , Diagnóstico por Imagen/instrumentación , Microbiología de Alimentos , Humanos , Infecciones por Salmonella
13.
Int J Cancer ; 127(9): 2129-37, 2010 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-20143391

RESUMEN

T-box-containing protein expressed in T cells (T-bet) is a master transcription factor for the development of interferon (IFN) gamma-producing T helper 1 (Th1) cells and also functions in other immune cells including natural killer (NK), cytotoxic T lymphocytes and dendritic cells. T-bet-deficient mice increased susceptibility to viral infection and tumor development due to the defective functions of immune cells. T-bet is known to play a key role in NK-mediated antimetastatic response; however, it remains to be characterized whether T-bet is essential for in vivo tumor suppression mediated by T cells. Here, we have investigated in vivo tumor suppression effect of T-bet-restored T cells using T cell-specific and inducible T-bet transgenic mice generated in a T-bet-deficient background. T-bet-null mice increased susceptibility to tumor development, whereas induction of T cell-specific T-bet expression upon melanoma cell injection substantially suppressed tumor development by inducing IFNgamma production in T cells and tumor cell apoptosis. Late induction of T-bet expression in tumor-bearing mice produced comparable amounts of IFNgamma with control and significantly decreased tumor volume. In addition, increased melanoma lung metastasis in T-bet-deficient mice was strikingly inhibited by T-bet restoration in T cells. Intravenous injection of activated Th1 cells, not T-bet-null Th1 cells, attenuated metastatic melanoma progression, in addition, restoration of T-bet in T-bet-null Th1 cells certainly retrieved antimetastatic activity. These results suggest that T-bet expression in T cells is crucial for the control of tumor development and antimetastatic activity.


Asunto(s)
Melanoma Experimental/inmunología , Neoplasias Cutáneas/inmunología , Proteínas de Dominio T Box/metabolismo , Linfocitos T/metabolismo , Animales , Melanoma Experimental/patología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ratones Transgénicos , Metástasis de la Neoplasia , Trasplante de Neoplasias , Proteínas de Dominio T Box/deficiencia , Linfocitos T Colaboradores-Inductores/metabolismo
14.
Biochem Biophys Res Commun ; 394(3): 811-6, 2010 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-20233578

RESUMEN

G12 family have been known to modulate a variety of cellular events such as cell migration, B cell activation and maturation, cytokine production, and cell differentiation. In particular, Galpha12 modulates IgG production, thus induces IgG antibody-mediated immune responses. However, it is largely unknown whether Galpha12 is required for T cell-mediated immune functions. In this study, we investigated the effects of Galpha12 in the activation and differentiation of CD4+ T cells. While PMA plus ionomycin induced equal levels of IL-2 production in WT and Galpha12-deficient lymphocytes, TCR-triggered IL-2 production was significantly attenuated in Galpha12 KO lymphocytes. In particular, CD4+ T cells and effector Th cells lacking of Galpha12 revealed diminished IL-2 production, but not IFNgamma production, upon TCR stimulation. In addition, supplement of IL-2 preferentially induced Galpha12-deficient CD4+ T cells into Th2 and Th17 cells; however, the expression of specific transcription factors was unchanged in Galpha12 KO Th cells. While IL-2 expression was still diminished by the re-stimulation with anti-CD3, PMA plus ionomycin restored IL-2 production in Galpha12-deficient Th1 and Th2 cells. These results suggest that Galpha12 may be a critical signaling molecule in TCR-induced IL-2 production and also relay a signal to suppress Th2 and Th17 cell differentiation.


Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP G12-G13/fisiología , Interleucina-17/inmunología , Interleucina-2/biosíntesis , Linfocitos T Colaboradores-Inductores/inmunología , Células Th2/inmunología , Animales , Antígenos CD4/inmunología , Diferenciación Celular , Subunidades alfa de la Proteína de Unión al GTP G12-G13/genética , Interferón gamma/biosíntesis , Activación de Linfocitos , Ratones , Ratones Noqueados
15.
J Allergy Clin Immunol ; 123(2): 479-85, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19081613

RESUMEN

BACKGROUND: A T(H)1-specific transcription factor, T-box-containing protein expressed in T cells (T-bet), controls the production of both T(H)1 and T(H)2 cytokines in T(H) cell differentiation by means of distinct mechanisms. T-bet-deficient mice overproduce T(H)2 cytokines and have spontaneous airway inflammation. OBJECTIVES: We tested whether T-bet overexpression could protect against the development or progression of asthma. METHODS: We generated a T cell-specific and inducible line of T-bet-transgenic mice on a T-bet-deficient genetic background and used it to study the function of T-bet in an ovalbumin (OVA)-induced asthma model. RESULTS: Induction of T-bet in a T cell-specific manner in an OVA model of asthma concomitant with OVA injection prevented airway hyperresponsiveness, eosinophilic and lymphocytic inflammation, and IL-5 and IL-13 production in bronchoalveolar lavage fluid and also reduced serum IgE and T(H)2 cytokine production by peripheral T cells. Even when T-bet expression was induced during later stages of asthma progression, T-bet overexpression still attenuated airway hyperresponsiveness and goblet cell hyperplasia, as well as T(H)2 cytokine production. CONCLUSIONS: Our results suggest that T-bet expression in T cells can prevent the initiation of airway inflammation and progression of chronic inflammation and might be extrapolated to human asthma.


Asunto(s)
Asma/inmunología , Citocinas/inmunología , Proteínas de Dominio T Box/metabolismo , Linfocitos T/inmunología , Células Th2/inmunología , Alérgenos/inmunología , Animales , Asma/metabolismo , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Doxiciclina/farmacología , Eosinofilia/inmunología , Eosinofilia/metabolismo , Células Caliciformes/inmunología , Células Caliciformes/patología , Inmunoglobulina E/sangre , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Ovalbúmina/inmunología , Proteínas de Dominio T Box/genética , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Células Th2/efectos de los fármacos , Células Th2/metabolismo
16.
Br J Haematol ; 146(3): 270-81, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19500098

RESUMEN

Bortezomib is a therapeutic proteasome inhibitor with antimyeloma activity and polyphenols are well known compounds that exert antiproliferative effects against tumuors. We attempted to co-treat myeloma cells with bortezomib and polyphenols, anticipating a synergistic effect. However, the anticancer activity of bortezomib was blocked by the polyphenols. The structural features of the polyphenols correlated strikingly with their antagonistic effect; in particular, the presence or absence of a vicinal diol moiety was the key element for effective blockage of the anticancer function of bortezomib. We speculated that the vicinal diols in the polyphenols interact with the boronic acid of bortezomib and convert the active triangular boronic acid of bortezomib to an inactive tetrahedral boronate, thus abolishing the antimyeloma activity of bortezomib. We confirmed this hypothesis by (11)B nuclear magnetic resonance spectroscopy and an in vitro assay on multiple myeloma (MM) cell lines and primary myeloma cells from patients. Based on these findings, restriction of the intake of natural polyphenols in foods or vitamin supplements during bortezomib treatment in MM patients should be considered.


Asunto(s)
Antineoplásicos/antagonistas & inhibidores , Ácidos Borónicos/antagonistas & inhibidores , Flavonoides/farmacología , Mieloma Múltiple/dietoterapia , Fenoles/farmacología , Pirazinas/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Bortezomib , Proliferación Celular/efectos de los fármacos , Interacciones Farmacológicas , Humanos , Polifenoles
17.
Biochem Biophys Res Commun ; 385(2): 204-9, 2009 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-19450563

RESUMEN

Sauchinone, a lignan compound isolated from the root of Saururus chinensis, has been recently demonstrated to exhibit anti-inflammatory activity via the suppression of NF-kB p65 activity in vitro. In an effort to evaluate the in vivo anti-inflammatory function of sauchinone, we have evaluated the effects of sauchinone on allergen-induced airway inflammation using a murine model of allergic asthma. We observed that marked eosinophilic and lymphocyte infiltration in the BAL fluid were suppressed to a significant degree by sauchinone, and that mucus-secreting goblet cell hyperplasia and collagen deposition in the airways were also ameliorated by administration of sauchinone treatment. Moreover, gene expression of the inflammatory cytokines, IL-13, and IL-5 and eotaxin in the lung, and IL-5 in the draining lymph node were significantly decreased in sauchinone-treated mice. We demonstrated that sauchinone repressed Th2 cell development in vitro and IL-4 production by Th2 cells, and also inhibited GATA-3-mediated IL-5 promoter activity in a dose-dependent manner. Collectively, sauchinone ameliorated allergen-induced airway inflammation, in part, by repressing GATA-3 activity for Th2 cell development, indicating the possible therapeutic potential of sauchinone in airway inflammatory diseases including allergic asthma and rhinitis.


Asunto(s)
Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Benzopiranos/uso terapéutico , Dioxoles/uso terapéutico , Terapia de Inmunosupresión , Rinitis Alérgica Perenne/tratamiento farmacológico , Células Th2/efectos de los fármacos , Alérgenos , Animales , Asma/inmunología , Quimiocina CCL11/genética , Factor de Transcripción GATA3/metabolismo , Expresión Génica/efectos de los fármacos , Células Caliciformes/efectos de los fármacos , Células Caliciformes/metabolismo , Interleucina-13/genética , Interleucina-15/genética , Interleucina-4/genética , Interleucina-5/genética , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/inmunología , Ratones , Ratones Endogámicos BALB C , Regiones Promotoras Genéticas/efectos de los fármacos , Rinitis Alérgica Perenne/inmunología , Células Th2/inmunología
18.
Surg Oncol ; 27(1): 106-113, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29549897

RESUMEN

BACKGROUND: We screened resected tumor tissues from patients with lung cancer for EGFR mutations, ALK rearrangements, and rearranged during transfection (RET) gene variants (including RET rearrangements and the Kinesin Family Member 5B (KIF5B)-RET fusion gene) using various methods including reverse transcription polymerase chain reaction (RT-PCR), transcript assays, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). We also examined the protein expression of associated downstream signaling molecules to assess the effect of these variants on patient outcome. METHOD: We constructed a tissue microarray (TMA) comprising 581 resected tumor tissues from patients with lung adenocarcinoma and analyzed the microarray by both FISH (using RET break-apart and KIF5B-RET SY translocation probes) and a commercial RET transcript assay. We evaluated the expression of RET and RET-related signaling molecules, including p-AKT and p-ERK, by TMA -based IHC staining. RESULTS: Among the 581 specimens, 51 (8.8%) specimens harbored RET rearrangements, including 12 cases (2.1%) carrying a KIF5B-RET fusion gene. Surprisingly, RET expression was lower in KIF5B-RET fusion gene-positive than in RET wild-type specimens. We detected activating EGFR mutations in 11 (21.6%) of the 51 RET variant-positive specimens. Among the KIF5B-RET fusion gene-positive specimens, p-ERK expression was significantly lower in the EGFR mutation subgroup showing RET expression than in the EGFR mutation subgroup that did not express RET. Similarly, the RET rearrangement group showed significant variation in the expression level of p-AKT (P = 0.028) and p-ERK, whose expression remarkably increased in specimens not expressing RET. The expression of p-ERK markedly increased in the RET rearrangement group regardless of RET expression. CONCLUSION: This result suggests that a combination of RET and ERK inhibitors may be an effective treatment strategy for lung adenocarcinoma patients harboring RET variants.


Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Reordenamiento Génico , Neoplasias Pulmonares/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas c-ret/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Receptores ErbB/genética , Femenino , Estudios de Seguimiento , Células HEK293 , Humanos , Neoplasias Pulmonares/patología , Masculino , Ratones , Persona de Mediana Edad , Mutación , Células 3T3 NIH , Pronóstico , Translocación Genética , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto Joven
19.
Otolaryngol Head Neck Surg ; 137(4): 636-41, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17903583

RESUMEN

OBJECTIVES: To evaluate the necessity of preserving the posterior branch of the great auricular nerve during parotidectomy. STUDY DESIGN AND SETTING: Forty-six patients undergoing parotidectomy were prospectively analyzed. Twenty-four patients had preservation of the posterior branch of the great auricular nerve; in the remaining 22 patients the nerve was sacrificed. A sensory index score was defined as the area involved multiplied by the intensity grade of sensory loss. Quality-of-life was evaluated with a questionnaire. RESULTS: The sensory index score was significantly higher in the sacrificed group as compared with the preserved group at both 1 week (41.87 vs 62.11) and 1 month (24.91 vs 46.11) after parotidectomy. The sensory deficit improved over time in both groups, and after 12 months only minimal sensory loss remained. Quality-of-life was not significantly different between the groups. CONCLUSIONS: Irrespective of preservation of the posterior branch of the great auricular nerve, sensory deficit improved over time. Therefore, preservation of the posterior branch of the great auricular nerve might not be necessary during parotidectomy.


Asunto(s)
Oído Externo/inervación , Enfermedades de las Parótidas/cirugía , Glándula Parótida/inervación , Neoplasias de la Parótida/cirugía , Adenolinfoma/cirugía , Adenoma Pleomórfico/cirugía , Adolescente , Adulto , Anciano , Plexo Cervical/cirugía , Niño , Femenino , Estudios de Seguimiento , Granuloma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Glándula Parótida/cirugía , Estudios Prospectivos , Calidad de Vida , Sensación/fisiología , Trastornos de la Sensación/etiología , Umbral Sensorial/fisiología , Tacto/fisiología
20.
Otolaryngol Head Neck Surg ; 135(3): 404-8, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16949972

RESUMEN

OBJECTIVE: To evaluate the findings of computed tomography (CT) and histopathology of the bulla ethmoidalis as objective markers of bone remodeling in chronic rhinosinusitis (CRS). METHODS: Preoperative ostiomeatal unit (OMU) scans and histopathologic findings of the bulla ethmoidalis were performed on 23 patients (39 sides) undergoing endoscopic sinus surgery for CRS. Lund-Mackay scores and Hounsfield units (HU) of the bulla were checked in coronal CT scans. The pathologist graded the severities of the mucosal and bony changes in histopathology. Statistical analysis was performed using Mann-Whitney U test and Spearman correlation coefficient (r). RESULTS: The HU values of the bulla were significantly increased with higher Lund-Mackay scores in OMU CT (r = 0.405, P = 0.01). The bony grades in histopathology were significantly increased with higher mucosal grades (r = 0.821, P = 0.0001). These findings in CT scans and histopathology were well correlated with each other (r > 0.3, P < 0.05). CONCLUSION: HU may be a useful objective marker of bone remodeling in chronic rhinosinusitis.


Asunto(s)
Remodelación Ósea/fisiología , Rinitis/fisiopatología , Sinusitis/fisiopatología , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/patología , Resorción Ósea/fisiopatología , Enfermedad Crónica , Endoscopía , Hueso Etmoides/diagnóstico por imagen , Hueso Etmoides/patología , Hueso Etmoides/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Cavidad Nasal/diagnóstico por imagen , Cavidad Nasal/patología , Cavidad Nasal/fisiopatología , Mucosa Nasal/patología , Osteoblastos/patología , Osteoclastos/patología , Periostio/patología , Estudios Prospectivos , Estudios Retrospectivos , Rinitis/diagnóstico por imagen , Rinitis/patología , Sinusitis/diagnóstico por imagen , Sinusitis/patología
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