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Electrocardiogram (ECG) biometric provides an authentication to identify an individual on the basis of specific cardiac potential measured from a living body. Convolutional neural networks (CNN) outperform traditional ECG biometrics because convolutions can produce discernible features from ECG through machine learning. Phase space reconstruction (PSR), using a time delay technique, is one of the transformations from ECG to a feature map, without the need of exact R-peak alignment. However, the effects of time delay and grid partition on identification performance have not been investigated. In this study, we developed a PSR-based CNN for ECG biometric authentication and examined the aforementioned effects. Based on a population of 115 subjects selected from the PTB Diagnostic ECG Database, a higher identification accuracy was achieved when the time delay was set from 20 to 28 ms, since it produced a well phase-space expansion of P, QRS, and T waves. A higher accuracy was also achieved when a high-density grid partition was used, since it produced a fine-detail phase-space trajectory. The use of a scaled-down network for PSR over a low-density grid with 32 × 32 partitions achieved a comparable accuracy with using a large-scale network for PSR over 256 × 256 partitions, but it had the benefit of reductions in network size and training time by 10 and 5 folds, respectively.
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Arritmias Cardíacas , Redes Neurales de la Computación , Humanos , Arritmias Cardíacas/diagnóstico , Frecuencia Cardíaca , Biometría , Electrocardiografía/métodos , AlgoritmosRESUMEN
Vaccinia mature virus requires A26 envelope protein to mediate acid-dependent endocytosis into HeLa cells in which we hypothesized that A26 protein functions as an acid-sensitive membrane fusion suppressor. Here, we provide evidence showing that N-terminal domain (aa1-75) of A26 protein is an acid-sensitive region that regulates membrane fusion. Crystal structure of A26 protein revealed that His48 and His53 are in close contact with Lys47, Arg57, His314 and Arg312, suggesting that at low pH these His-cation pairs could initiate conformational changes through protonation of His48 and His53 and subsequent electrostatic repulsion. All the A26 mutant mature viruses that interrupted His-cation pair interactions of His48 and His 53 indeed have lost virion infectivity. Isolation of revertant viruses revealed that second site mutations caused frame shifts and premature termination of A26 protein such that reverent viruses regained cell entry through plasma membrane fusion. Together, we conclude that viral A26 protein functions as an acid-sensitive fusion suppressor during vaccinia mature virus endocytosis.
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Endocitosis , Fusión de Membrana , Virus Vaccinia/metabolismo , Proteínas Virales/metabolismo , Internalización del Virus , Animales , Chlorocebus aethiops , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Ratones , Virus Vaccinia/genética , Proteínas Virales/genéticaRESUMEN
UNLABELLED: Recurrent cancer genome aberrations are indicators of residing crucial cancer genes. Although recent advances in genomic technologies have led to a global view of cancer genome aberrations, the identification of target genes and biomarkers from the aberrant loci remains difficult. To facilitate searches of cancer genes in human hepatocellular carcinoma (HCC), we established a comprehensive protocol to analyze copy number alterations (CNAs) in cancer genomes using high-density single nucleotide polymorphism arrays with unpaired reference genomes. We identified common HCC genes by overlapping the shared aberrant loci in multiple cell lines with functional validation and clinical implications. A total of 653 amplicons and 57 homozygous deletions (HDs) were revealed in 23 cell lines. To search for novel HCC genes, we overlapped aberrant loci to uncover 6 HDs and 126 amplicons shared by at least two cell lines. We selected two novel genes, fibronectin type III domain containing 3B (FNDC3B) at the 3q26.3 overlapped amplicon and solute carrier family 29 member 2 (SLC29A2) at the 11q13.2 overlapped amplicon, to investigate their aberrations in HCC tumorigenesis. Aberrant up-regulation of FNDC3B and SLC29A2 occurred in multiple HCC data sets. Knockdown of these genes in amplified cells decreased cell proliferation, anchorage-independent growth, and tumor formation in xenograft models. Importantly, up-regulation of SLC29A2 in HCC tissues was significantly associated with advanced stages (P = 0.0031), vascular invasion (P = 0.0353), and poor patient survival (P = 0.0325). Overexpression of FNDC3B or SLC29A2 in unamplified HCC cells promoted cell proliferation through activation of the signal transducer and activator of transcription 3 signaling pathway. CONCLUSION: A standardized genome-wide CNA analysis protocol using data from user-generated or public domains normalized with unpaired reference genomes has been established to facilitate high-throughput detection of cancer genes as significant target genes and biomarkers for cancer diagnosis and therapy.
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Carcinoma Hepatocelular/genética , Genes Relacionados con las Neoplasias/genética , Genoma , Neoplasias Hepáticas/genética , Mutación , Polimorfismo de Nucleótido Simple , Animales , Carcinoma Hepatocelular/patología , División Celular , Línea Celular Tumoral , Aberraciones Cromosómicas , Ensayo de Unidades Formadoras de Colonias , Técnicas de Silenciamiento del Gen , Genotipo , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/patología , Ratones , Ratones Desnudos , Recurrencia Local de Neoplasia/genética , Interferencia de ARNRESUMEN
The technique of Hadamard transform was successfully coupled with GC/nonresonant multiphoton ionization/TOFMS, for the first time. 1,4-Dichlorobenzene and the fourth harmonic generation (266 nm) of a Nd:YAG laser were employed as a model sample and an ionization laser, respectively. A Hadamard-injector coupled with a capillary-based supersonic jet nozzle (capillary-injector) was also developed in this study. The Hadamard-injector was used to obtain the chromatogram, which was encoded by successive sample introduction based on Hadamard codes, and the capillary-injector was used for injection of GC-elutes into TOFMS. Compared with a conventional single injection method, the S/N ratios were substantially improved after inverse Hadamard transformation of the encoded chromatogram. Under optimized conditions, when Hadamard matrices of 103 and 255 were used, the S/N ratios of the signals for 1,4-dichlorobenzene (concentration level, 4 microg/1 mL ACN) were substantially improved to 4.1- and 6.6-fold, respectively, and those improvements are in good agreement with those obtained by theory (5.1- and 8.0-fold).
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B-cell translocation gene 3 (BTG3) is a member of the antiproliferative BTG gene family and is a downstream target of p53. Here, we show that senescence triggered by BTG3 depletion was accompanied by a secretome enriched with cytokines, growth factors, and matrix-remodeling enzymes, which could promote angiogenesis and cell scattering in vitro. We present evidence that at least part of these activities can be explained by elevated HIF-1α activity. Mechanistically, the BTG3 C-terminal domain competes with the coactivator p300 for binding the HIF-1α transactivation domain. The angiogenic promoting effect of BTG3 knockdown was largely diminished upon co-depletion of HIF-1α, indicating that HIF-1α is a major downstream target of BTG3 in the control of angiogenesis. In vivo, ectopic expression of BTG3 suppresses angiogenesis in xenograft tumors; and syngenic tumor growth and metastasis were enhanced in Btg3-null mice. Moreover, analysis of clinical datasets revealed that a higher BTG3/VEGFA expression ratio correlates with improved patient survival in a number of cancer types. Taken together, our findings highlight the non-autonomous regulation of tumor microenvironment by BTG3 while suppressing tumor progression.
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Proteínas de Ciclo Celular/deficiencia , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Microambiente Tumoral , Proteínas Supresoras de Tumor/deficiencia , Animales , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Proliferación Celular/genética , Senescencia Celular , Fibroblastos/metabolismo , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Ratones , Neoplasias/irrigación sanguínea , Neoplasias/genética , Neoplasias/patología , Neovascularización Fisiológica , Unión Proteica , Análisis de Supervivencia , Microambiente Tumoral/genética , Proteínas Supresoras de Tumor/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Autonomous secretion of aldosterone in patients with primary aldosteronism increases glomerular filtration rate and causes kidney damage. The influence of a mild decrease in kidney function on residual hypertension after adrenalectomy is unexplored. STUDY DESIGN: Nonconcurrent prospective study. SETTING & PARTICIPANTS: The study was based on the Taiwan Primary Aldosteronism Investigation (TAIPAI) database. 150 patients (61 men; overall mean age, 47.2 +/- 11.6 years) with a diagnosis of aldosterone-producing adenoma had undergone unilateral adrenalectomy at National Taiwan University Hospital from July 1999 to January 2007. PREDICTOR: Presurgery estimated glomerular filtration rate (eGFR). OUTCOMES & MEASUREMENTS: Residual hypertension after adrenalectomy, defined either as less than 75% of recorded blood pressure measurements with systolic blood pressure less than 140 mm Hg and diastolic blood pressure less than 90 mm Hg or requiring antihypertensive medications during the first year after surgery. RESULTS: Before surgery, 27 (18%), 72 (48%), and 51 (34%) patients had moderately to severely decreased (<60 mL/min/1.73 m(2)), mildly decreased (60
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Adenoma/fisiopatología , Neoplasias de la Corteza Suprarrenal/fisiopatología , Adrenalectomía , Aldosterona/sangre , Tasa de Filtración Glomerular , Hipertensión/fisiopatología , Riñón/fisiopatología , Adenoma/sangre , Adenoma/complicaciones , Adenoma/metabolismo , Adenoma/cirugía , Neoplasias de la Corteza Suprarrenal/sangre , Neoplasias de la Corteza Suprarrenal/complicaciones , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/cirugía , Adulto , Aldosterona/metabolismo , Presión Sanguínea , Creatinina/sangre , Femenino , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/etiología , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/fisiopatología , Hipertensión/sangre , Hipertensión/etiología , Hipertensión/metabolismo , Riñón/metabolismo , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Successful application of the Hadamard transform (HT) technique to gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) is described. Novel sample injection devices were developed to achieve multiple sample injections in both GC and LC instruments. Air pressure was controlled by an electromagnetic valve in GC, while a syringe pump and Tee connector were employed for the injection device in LC. Two well-known, abused drugs, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and N, N-dimethyltryptamine (DMT), were employed as model samples. Both of the injection devices permitted precise successive injections, resulting in clearly modulated chromatograms encoded by Hadamard matrices. After inverse Hadamard transformation of the encoded chromatogram, the signal-to-noise (S/N) ratios of the signals were substantially improved compared with those expected from theoretical values. The S/N ratios were enhanced approximately 10-fold in HT-GC/MS and 6.8 in HT-LC/MS, using the matrices of 1023 and 511, respectively. The HT-GC/MS was successfully applied to the determination of MDMA in the urine sample of a suspect.
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Wastewater effluent from textile plants using various dyes is one of the major water pollutants to the environment. Traditional chemical, physical and biological processes for treating textile dye wastewaters have disadvantages such as high cost, energy waste and generating secondary pollution during the treatment process. The photocatalytic process using TiO2 semiconductor particles under UV light illumination has been shown to be potentially advantageous and applicable in the treatment of wastewater pollutants. In this study, the dye decomposition kinetics by nano-size TiO2 suspension at natural solution pH was experimentally studied by varying the agitation speed (50-200 rpm), TiO2 suspension concentration (0.25-1.71 g/L), initial dye concentration (10-50 ppm), temperature (10-50 degrees C), and UV power intensity (0-96 W). The experimental results show the agitation speed, varying from 50 to 200 rpm, has a slight influence on the dye decomposition rate and the pH history; the dye decomposition rate increases with the TiO2 suspension concentration up to 0.98 g/L, then decrease with increasing TiO2 suspension concentration; the initial dye decomposition rate increases with the initial dye concentration up to a certain value depending upon the temperature, then decreases with increasing initial dye concentration; the dye decomposition rate increases with the UV power intensity up to 64 W to reach a plateau. Kinetic models have been developed to fit the experimental kinetic data well.
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Colorantes/química , Industria Textil/métodos , Purificación del Agua/instrumentación , Purificación del Agua/métodos , Diseño de Equipo , Concentración de Iones de Hidrógeno , Residuos Industriales , Cinética , Modelos Químicos , Fotoquímica , Temperatura , Textiles , Factores de Tiempo , Titanio/química , Eliminación de Residuos Líquidos , Contaminantes Químicos del AguaRESUMEN
OBJECTIVE: Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. However, the reversibility of cardiac fibrosis is still unclear. Our objective was to investigate myocardial fibrosis in primary aldosteronism patients and its change after surgery. METHOD: We prospectively analyzed 20 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008 and 20 patients with essential hypertension were enrolled as the control group. Plasma carboxy-terminal propeptide of procollagen type I (PICP) determination and echocardiography including ultrasonic tissue characterization by cyclic variation of integrated backscatter (CVIBS) were performed in both groups and 1 year after operation in the APA group. RESULTS: APA patients had significantly higher SBP and DBP, higher plasma aldosterone concentration (PAC), higher aldosterone-renin ratio (ARR), lower serum potassium levels, and lower plasma renin activity (PRA) than patients with essential hypertension. In echocardiography, APA patients had a higher left ventricular mass index than essential hypertension patients. APA patients had significantly lower CVIBS (6.2 ± 1.5 vs. 8.7 ± 2.0 dB, P < 0.001) and higher plasma PICP levels (107 ± 27 vs. 85 ± 24 µg/l, P = 0.009) than essential hypertension patients. In the correlation study, CVIBS is correlated with log-transformed PRA and log-transformed ARR and PICP is correlated with log-transformed PRA, log-transformed PAC, and log-transformed ARR. One year after adrenalectomy, CVIBS increased significantly (6.2 ± 1.5 to 7.3 ± 1.7 dB, P = 0.033) and plasma PICP levels decreased (107 ± 27 vs. 84 ± 28 µg/l, P = 0.026). CONCLUSION: Increases in collagen content in the myocardium of APA patients may be reversed by adrenalectomy.
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Adrenalectomía , Cardiomiopatías/prevención & control , Hiperaldosteronismo/cirugía , Hipertrofia Ventricular Izquierda/prevención & control , Adenoma/complicaciones , Adenoma/patología , Adenoma/cirugía , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/cirugía , Aldosterona/sangre , Cardiomiopatías/diagnóstico , Cardiomiopatías/etiología , Ecocardiografía , Femenino , Fibrosis/prevención & control , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hipertensión/etiología , Hipertensión/patología , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/etiología , Masculino , Persona de Mediana Edad , Miocardio/patología , Fragmentos de Péptidos , Potasio/sangre , Procolágeno , Estudios Prospectivos , Renina/sangre , Resultado del TratamientoRESUMEN
BACKGROUND: Though aldosterone-renin ratio (ARR) is the current routine screening method for suspicious primary aldosteronism, we hypothesized that the simple formula combining body mass index (BMI) and serum potassium to urine potassium clearance (PUKC) ratio was comparable to ARR. METHODS: Records of patients who were referred to the National Taiwan University Hospital for investigation of primary aldosteronism from January 1995 through December 2007 were retrieved. Primary aldosteronism was diagnosed based on the modified 4-corners criteria, otherwise essential hypertension was diagnosed. In both groups, the PUKC/BMI ratio was determined as well as the ARR. Bland-Altman and mountain-plot analysis were used to validate the agreement between ARR and PUKC/BMI. Receiver operating characteristic (ROC) curves were used to compare the sensitivity and specificity of PUKC/BMI and ARR. RESULTS: The records for urinary potassium were analyzed for 177 hypertensive patients (134 patients with primary aldosteronism). ROC curves showed comparable areas under the curves of both methods (95% CI: -0.029 to 0.183; p=0.186). Bland-Altman analysis further supported the agreement between ARR and PUKC/BMI ratio. CONCLUSIONS: We found that the screening power of PUKC/BMI was as good as that of conventional ARR. With the quick and extensive availability of the PUKC/BMI method and its equivalence to ARR, this screening strategy would be a good first-line tool for massive community-based primary aldosteronism surveys.
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Índice de Masa Corporal , Hiperaldosteronismo/diagnóstico , Potasio/sangre , Potasio/orina , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios RetrospectivosRESUMEN
OBJECTIVES: To obtain information about the effect of prolonged aldosterone excess on kidney function. METHODS: We determined kidney function changes defined by cystatin C-based estimations of glomerular filtration rate (CysC-GFR). Pretreatment proteinuria and intrarenal Doppler velocimetric indices in primary aldosteronism were examined and followed after adrenalectomy or spironolactone treatment. RESULTS: This prospective, multicenter study included 130 primary aldosteronism patients (56 men; age, 49.9 ± 13.4 years: 100 with adenoma and 30 with idiopathic hyperaldosteronism) and 73 essential hypertension patients (36 men; age, 51.4 ± 14.8 years) as controls. Patients with primary aldosteronism had higher CysC-GFR (P < 0.05) and heavier proteinuria (0.042) than those with essential hypertension. With primary aldosteronism, a higher aldosterone-renin ratio (odds ratio, OR = 7.85, P = 0.008) was independently related to pretreatment CysC-GFR. The factors related to pretreatment proteinuria included CysC-GFR (OR, -0.006, P = 0.001), plasma aldosterone concentration (OR, 0.004, P = 0.002), and duration of hypertension (OR, 0.016, P = 0.032). Duration of hypertension was also independently correlated with the pretreatment resistive index among primary aldosteronism patients (OR, 0.004, P = 0.035). CysC-GFR (all, P < 0.05), proteinuria (P < 0.001), and resistive index (P < 0.001) decreased 1 year after adrenalectomy but not with spironolactone treatment. CONCLUSION: Our data suggest that prolonged hyperaldosteronism will cause relative kidney hyperfiltration and reversible intrarenal vascular structural changes, which disguise the consequent renal injury, including declining GFR and proteinuria. Adrenalectomy and spironolactone treatment exert different clinical impacts toward kidney damage even with a similar blood pressure-lowering effect.
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Cistatina C/fisiología , Hiperaldosteronismo/fisiopatología , Hiperaldosteronismo/terapia , Riñón/fisiopatología , Proteinuria/fisiopatología , Adulto , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Kidney impairment is noted in primary aldosteronism (PA), and probably initiated by glomerular hyperfiltration. METHODS: A prospectively defined survey was conducted on 602 patients who were suspected of PA in the multiple-center Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Estimated glomerular filtration rate (eGFR) was calculated and followed up at 1 yr after treatment. RESULTS: The diagnosis of PA was confirmed in 330 patients. Among them 17% of these patients had kidney impairment (eGFR<60 ml/min/1.73 m²). Patients with PA had a higher prevalence of estimated hyperfiltration than those with essential hypertension (EH) (14.5% vs. 7.0%, p=0.005). The eGFR independently predicted PA (OR, 1.017) in the propensity-adjusted multivariate logistic model. In PA, plasma renin activity and lower serum potassium (p=0.018) was correlated with kidney impairment (p=0.001), while this relationship was not significant in patients with EH. Either unilateral adrenalectomy or treatment of spironolactone for PA patients caused a decrease of eGFR (p<0.001). Pre-operative hypokalemia (p=0.013) and the long latency of hypertension (p=0.016) could enhance the significant decrease of eGFR after adrenalectomy. CONCLUSIONS: Patients with aldosteronism had relative estimated hyperfiltration than patients with EH. Calculation of eGFR may increase the specificity in identifying patients with PA. Our findings demonstrate the correlation of serum potassium and renin with estimated hyperfiltration in PA and their relationship to kidney damage. These results provide a high priority for future renal protective strategies and methods for the early diagnosis and prompt treatment of PA.
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Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/fisiopatología , Enfermedades Renales/complicaciones , Enfermedades Renales/fisiopatología , Tasa de Filtración Glomerular , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamiento farmacológico , Hipertensión/fisiopatología , Modelos Logísticos , Persona de Mediana Edad , Potasio/sangre , Estudios Prospectivos , Renina/sangre , Espironolactona/uso terapéuticoRESUMEN
OBJECTIVE: Current data on primary aldosteronism (PA) from Asian populations are scarce. This cohort study clarifies the attributes of patients with PA in a typical Chinese population. DESIGN: An observational cohort study. METHODS: The records of patients referred to the Hypertension Clinic from a multi-centre registration in Taiwan from January 1995 to December 2007 were reviewed. All patients with PA were classified into two subtypes: aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism (IHA); their characteristics were compared. RESULTS: Our cohort consisted of 346 patients with PA, 255 with APA and 91 with IHA. The initial hypokalaemia (59% in APA vs. 27.5% in IHA, p < 0.0001) and transtubular potassium gradient (TTKG) (6.30 ± 2.41 in APA vs. 4.91 ± 2.03 in IHA, p = 0.01) were higher in the APA group. Baseline plasma aldosterone concentration (PAC) was also significantly different between the two subgroups (49.96 ± 38.15 ng/dl in APA vs. 34.24 ± 21.47 in IHA, p < 0.0001). CONCLUSIONS: In typical Chinese PA patients, the APA subgroup had a higher proportion of hypokalaemia with elevated TTKG and higher PAC as compared with the IHA subgroup. This largest Asian database also demonstrated major differences between the Caucasian and Chinese populations including female predilection, frequent hypokalaemia, and common paralytic myopathy.
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Hiperaldosteronismo/epidemiología , Adenoma/sangre , Adenoma/complicaciones , Adenoma/epidemiología , Aldosterona/sangre , Estudios de Cohortes , Demografía , Femenino , Humanos , Hiperaldosteronismo/clasificación , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hipertensión/sangre , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Masculino , Tamizaje Masivo , Prevalencia , Reproducibilidad de los Resultados , TaiwánRESUMEN
A novel Hadamard transform-gas chromatography/mass spectrometry (HT-GC/MS) system equipped with on-line sample collection systems is described. A Hadamard-injector was successfully designed and then coupled with an on-line adsorption/desorption system for detecting volatile organic compounds (VOCs) and a supercritical fluid extraction (SFE) system, respectively, by HT-GC/MS. Six VOCs and three pesticides were used as model compounds. In the former case, an activated-charcoal trap was used to trap VOCs from the indoor air. After 10L of indoor air had passed through the trap, the condensed components were heated and simultaneously injected into the GC column through the Hadamard-injector, based on Hadamard codes. In a second experiment, a sample of rice was spiked with three types of pesticides and the sample then extracted using a commercially available supercritical fluid extractor. After extraction, the extracted components were transferred to a holding tank and simultaneously injected into the GC column also using the Hadamard-injector. The findings show that, in both cases, the combination of on-line sample collection methods and the use of the Hadamard transform resulted in improved sensitivity and detection. Compared to the single injection used in most GC/MS systems, the signal-to-noise (S/N) ratios were substantially improved after inverse Hadamard transformation of the encoded chromatogram.
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Cromatografía con Fluido Supercrítico/instrumentación , Cromatografía con Fluido Supercrítico/métodos , Análisis de Fourier , Cromatografía de Gases y Espectrometría de Masas/instrumentación , Cromatografía de Gases y Espectrometría de Masas/métodos , Compuestos Orgánicos Volátiles/análisis , Diseño de Equipo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: A common pharmacologic test for the diagnosis of primary aldosteronism (PA) is the administration of captopril to determine whether an abnormal plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio(ARR) persists, although active renin concentration (ARC) may offer advantages with regard to processing and standardization. METHODS: A prospective, head-to-head study was conducted between Feb 2008 and Dec 2008. One hundred and fourteen patients enrolled and received captopril to aid in the diagnosis of PA in the TAIPAI intervention. RESULTS: Fifty-one patients were diagnosed with PA. Post-captopril ARC was significantly correlated with PRA. The area under the receiver operating characteristic curve of the post-captopril ARR was not different in PRA vs ARC measurements. When post-captopril ARC-based ARR (ARR(ARC))>35.5 as the cut-off value, we obtained sensitivity of 75.0% and specificity of 86.4% to differentiate PA from essential hypertension. CONCLUSIONS: The correlation of individual PRA and ARC after administration of captopril was excellent; especially at the lower PRA levels. Post-captopril ARR(ARC) values used to diagnose PA are not different from post-captopril PRA-based (ARR(PRA)) values in patients without kidney, liver and heart failures. Primary aldosteronism can be diagnosed with a post-captopril cut-off value of ARR(ARC)>35.5 pmol/ng.
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Aldosterona/sangre , Captopril , Hiperaldosteronismo/diagnóstico , Renina/sangre , Adulto , Anciano , Área Bajo la Curva , Diagnóstico Diferencial , Femenino , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/fisiopatología , Hipertensión/diagnóstico , Hipertensión/etiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Sensibilidad y EspecificidadRESUMEN
The purpose of this research was to pursuit the quantification of microbial degradation capacity for 2,4-dichlorophenoxyacetic acid (2,4-D) by detecting and quantifying a prominent 2,4-D degradation encoding plasmid. Batch reactor acclimation, de-acclimation, and re-acclimation tests were conducted during which periods the courses of 2,4-D dissipation and plasmid evolution were quantitatively measured. Pure cultures of bacterial strains were detected to give rise to a plasmid approximately the size of 90 kb after acclimation. The 90 kb plasmid content of Arthrobacter sp. increased when degradation occurred after acclimation, with a rate that corresponded closely to the degradation rate. During de-acclimation, plasmid content declined exponentially at a half-life of approximately 3.5 days. Re-acclimation saw a renewed induction of plasmid, but substrate consumption limited the rise of plasmid to a level much lower than after the first acclimation. This research recommends a method for measuring the microbial degradation capability for a xenobiotic.
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Ácido 2,4-Diclorofenoxiacético/metabolismo , Ácido 2,4-Diclorofenoxiacético/farmacología , Adaptación Fisiológica/efectos de los fármacos , Adaptación Fisiológica/genética , Bacterias Aerobias/fisiología , ADN Bacteriano/genética , Plásmidos/genética , Bacterias Aerobias/clasificación , Biodegradación Ambiental , ADN Bacteriano/efectos de los fármacos , Plásmidos/efectos de los fármacosRESUMEN
Breast cancer amplified sequence 2 (BCAS2) was reported previously as a transcriptional coactivator of estrogen receptor. Here, we report that BCAS2 directly interacts with p53 to reduce p53 transcriptional activity by mildly but consistently decreasing p53 protein in the absence of DNA damage. However, in the presence of DNA damage, BCAS2 prominently reduces p53 protein and provides protection against chemotherapeutic agent such as doxorubicin. Deprivation of BCAS2 induces apoptosis in p53 wild-type cells but causes G(2)-M arrest in p53-null or p53 mutant cells. There are at least two apoptosis mechanisms induced by silencing BCAS2 in wild-type p53-containing cells. Firstly, it increases p53 retention in nucleus that triggers the expression of apoptosis-related genes. Secondly, it increases p53 transcriptional activity by raising p53 phosphorylation at Ser(46) and decreases p53 protein degradation by reducing p53 phosphorylation at Ser(315). We show for the first time that BCAS2, a small nuclear protein (26 kDa), is a novel negative regulator of p53 and hence a potential molecular target for cancer therapy.
Asunto(s)
Neoplasias de la Mama/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis/fisiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Procesos de Crecimiento Celular/fisiología , Línea Celular Tumoral , Núcleo Celular/metabolismo , Daño del ADN , Humanos , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/deficiencia , Proteínas de Neoplasias/genética , Unión Proteica , Procesamiento Proteico-Postraduccional , Estructura Terciaria de Proteína , Activación Transcripcional , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: To assess whether angiotensin-II receptor blockers (ARBs) offer any additional advantage in confirming the diagnosis of primary aldosteronism (PA) and their use in the differentiation of PA subtypes. METHODS: A prospective, cohort, head-to-head study was conducted between July 2003 and July 2006. A total of 135 patients received captopril and losartan tests to confirm the diagnosis of PA in the TAIPAI (Taiwan Primary Aldosteronism Investigation) intervention. RESULTS: In total, 71 patients were diagnosed with PA. The area under the receiver-operating characteristic (ROC) curve of the postcaptopril plasma aldosterone concentration (PAC) was significantly less than that of the postlosartan PAC (0.744 vs. 0.829, P = 0.038). Using an aldosterone-renin ratio (ARR, ng/dl per ng/ml/h) >35 with a PAC >10 ng/dl, the specificity was 89.1% vs. 93.8% and the sensitivity was 66.2% vs. 84.5 % for the captopril test vs. the losartan test, respectively. With respect to the losartan test, the accuracy was 88.9%, the agreement was good (k = 0.778), and there was no disagreement with the McNemar test (P = 0.118). Losartan had the advantage of a better negative predictive value to exclude PA when patients were referred with a serum potassium (SK) level <3.8 mmol/l. When a postlosartan ARR >60 was the cutoff value, the positive predictive value was 82% with a negative predictive value of 57% in distinguishing aldosterone-producing adenomas (APAs) from idiopathic hyperaldosteronism (IHA). CONCLUSIONS: The postlosartan ARR and PAC were shown to have better accuracy for the diagnosis of PA than the captopril test. With a postlosartan ARR >60, APAs can be adequately differentiated from IHA.