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1.
Nano Lett ; 24(6): 1974-1980, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38316025

RESUMO

Hydrogen donor doping of correlated electron systems such as vanadium dioxide (VO2) profoundly modifies the ground state properties. The electrical behavior of HxVO2 is strongly dependent on the hydrogen concentration; hence, atomic scale control of the doping process is necessary. It is however a nontrivial problem to quantitatively probe the hydrogen distribution in a solid matrix. As hydrogen transfers its sole electron to the material, the ionization mechanism is suppressed. In this study, a methodology mapping the doping distribution at subnanometer length scale is demonstrated across a HxVO2 thin film focusing on the oxygen-hydrogen bonds using electron energy loss spectroscopy (EELS) coupled with first-principles EELS calculations. The hydrogen distribution was revealed to be nonuniform along the growth direction and between different VO2 grains, calling for intricate hydrogenation mechanisms. Our study points to a powerful approach to quantitatively map dopant distribution in quantum materials relevant to energy and information sciences.

2.
Nano Lett ; 22(21): 8654-8661, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36315005

RESUMO

Probabilistic computing has emerged as a viable approach to solve hard optimization problems. Devices with inherent stochasticity can greatly simplify their implementation in electronic hardware. Here, we demonstrate intrinsic stochastic resistance switching controlled via electric fields in perovskite nickelates doped with hydrogen. The ability of hydrogen ions to reside in various metastable configurations in the lattice leads to a distribution of transport gaps. With experimentally characterized p-bits, a shared-synapse p-bit architecture demonstrates highly parallelized and energy-efficient solutions to optimization problems such as integer factorization and Boolean satisfiability. The results introduce perovskite nickelates as scalable potential candidates for probabilistic computing and showcase the potential of light-element dopants in next-generation correlated semiconductors.

3.
Nanotechnology ; 33(12)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34852337

RESUMO

Nano-membrane tri-gateß-gallium oxide (ß-Ga2O3) field-effect transistors (FETs) on SiO2/Si substrate fabricated via exfoliation have been demonstrated for the first time. By employing electron beam lithography, the minimum-sized features can be defined with the footprint channel width of 50 nm. For high-quality interface betweenß-Ga2O3and gate dielectric, atomic layer-deposited 15 nm thick aluminum oxide (Al2O3) was utilized with tri-methyl-aluminum (TMA) self-cleaning surface treatment. The fabricated devices demonstrate extremely low subthreshold slope (SS) of 61 mV dec-1, high drain current (IDS) ON/OFF ratio of 1.5 × 109, and negligible transfer characteristic hysteresis. We also experimentally demonstrated robustness of these devices with current-voltage (I-V) characteristics measured at temperatures up to 400 °C.

4.
Small ; 15(40): e1903197, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418526

RESUMO

Single-atom catalysts are heterogeneous catalysts with atomistically dispersed atoms acting as a catalytically active center, and have recently attracted much attention owing to the minimal use of noble metals. However, a scalable and inexpensive support that can stably anchor isolated atoms remains a challenge due to high surface energy. Here, copper-halide polymer nanowires with sub-nanometer pores are proposed as a versatile support for single-atom catalysts. The synthesis of the nanowires is straightforward and completed in a few minutes. Well-defined sub-nanometer pores and a large free volume of the nanowires are advantageous over any other support material. The nanowires can anchor various atomistically dispersed metal atoms into the sub-nanometer pores up to ≈3 at% via a simple solution process, and this value is at least twice as big as previously reported data. The hydrogen evolution reaction activity of -18.0 A mgPt -1 at -0.2 V overpotential shows its potential for single-atom catalysts support.

5.
Korean J Parasitol ; 53(4): 465-70, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26323845

RESUMO

The present study was performed to report 15 anisakiasis cases in Korea and to review the Korean cases reported in the literature. Total 32 Anisakis type I larvae were detected in the stomach of 15 patients by the endoscopy. Single worm was detected from 12 cases, and even 9 larvae were found from 2 cases. Epigastric pain was most commonly manifested in almost all cases, and hemoptysis and hematemesis were seen in 1 case each. Symptom manifestations began at 10-12 hr after eating fish in 73.3% cases. Endoscopy was performed 1-2 days after the symptom onset in most cases. The common conger, Conger myriaster, was the probable infection source in 7 cases. In the review of Korean anisakiasis cases, thus far, total 645 cases have been reported in 64 articles. Anisakis type I larva was the most frequently detected (81.3%). The favorable infection site of larvae was the stomach (82.4%). The common conger was the most probable source of human infections (38.6%). Among the total 404 cases which revealed the age and sex of patients, 185 (45.8%) were males, and the remaining 219 (54.2%) were female patients. The age prevalence was the highest in forties (34.7%). The seasonal prevalence was highest in winter (38.8%). By the present study, 15 cases of gastric anisakiasis are added as Korean cases, and some epidemiological characteristics of Korean anisakiasis were clarified.


Assuntos
Anisaquíase/parasitologia , Anisaquíase/veterinária , Anisakis/isolamento & purificação , Doenças dos Peixes/parasitologia , Larva/fisiologia , Gastropatias/parasitologia , Adulto , Animais , Anisaquíase/epidemiologia , Anisakis/genética , Anisakis/fisiologia , Feminino , Peixes/classificação , Peixes/parasitologia , Contaminação de Alimentos/análise , Humanos , Larva/genética , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Estômago/parasitologia , Gastropatias/epidemiologia
6.
ACS Nano ; 18(3): 2105-2116, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38198599

RESUMO

Solid-state devices made from correlated oxides, such as perovskite nickelates, are promising for neuromorphic computing by mimicking biological synaptic function. However, comprehending dopant action at the nanoscale poses a formidable challenge to understanding the elementary mechanisms involved. Here, we perform operando infrared nanoimaging of hydrogen-doped correlated perovskite, neodymium nickel oxide (H-NdNiO3, H-NNO), devices and reveal how an applied field perturbs dopant distribution at the nanoscale. This perturbation leads to stripe phases of varying conductivity perpendicular to the applied field, which define the macroscale electrical characteristics of the devices. Hyperspectral nano-FTIR imaging in conjunction with density functional theory calculations unveils a real-space map of multiple vibrational states of H-NNO associated with OH stretching modes and their dependence on the dopant concentration. Moreover, the localization of excess charges induces an out-of-plane lattice expansion in NNO which was confirmed by in situ X-ray diffraction and creates a strain that acts as a barrier against further diffusion. Our results and the techniques presented here hold great potential for the rapidly growing field of memristors and neuromorphic devices wherein nanoscale ion motion is fundamentally responsible for function.

7.
Nat Commun ; 15(1): 4717, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830914

RESUMO

Materials with field-tunable polarization are of broad interest to condensed matter sciences and solid-state device technologies. Here, using hydrogen (H) donor doping, we modify the room temperature metallic phase of a perovskite nickelate NdNiO3 into an insulating phase with both metastable dipolar polarization and space-charge polarization. We then demonstrate transient negative differential capacitance in thin film capacitors. The space-charge polarization caused by long-range movement and trapping of protons dominates when the electric field exceeds the threshold value. First-principles calculations suggest the polarization originates from the polar structure created by H doping. We find that polarization decays within ~1 second which is an interesting temporal regime for neuromorphic computing hardware design, and we implement the transient characteristics in a neural network to demonstrate unsupervised learning. These discoveries open new avenues for designing ferroelectric materials and electrets using light-ion doping.

8.
Artigo em Inglês | MEDLINE | ID: mdl-37813815

RESUMO

Objective: To assess whether local anesthetic infiltration could minimize the carotid baroreceptor reflex (CBR) which has an incidence after carotid artery stenting (CAS) that varies from 29% to 51%. Methods: This retrospective single-center study included 51 patients (mean age, 70.47 years) who underwent CAS for carotid stenosis. The groups included patients who underwent CAS for asymptomatic ischemic stroke (n=41) or symptomatic disease (n=10). Preprocedural percutaneous lidocaine injections (PPLIs) were administered to 70.6% and 5.9% of patients who underwent elective CAS and emergency CAS, respectively. Results: Among patients who received PPLIs, the mean degree of stenosis was 80.5% (95% confidence interval [CI]: ±10.74, 51-98%). The mean distance from the common carotid artery bifurcation to the most stenotic lesion (CSD) was 8.3 mm (95% CI: ±0.97, 6.3-10.2 mm); the mean angle between the internal carotid artery and common carotid artery (CCA) trunk (IAG) was 65.6° (95% CI: ±2.39, 61-70°). Among patients who did not receive PPLIs, the mean degree of stenosis was 84.0% (95% CI: ±8.96, 70-99%). The mean CSD was 5.9 mm (95% CI: ±1.83, 1.9-9.9 mm); the mean IAG was 60.4° (95% CI: ±4.41, 51-70°). The procedure time was longer in the PPLI group than in the no PPLI group (28.19 [n=39] vs. 18.88 [n=12] days) (P=0.057); the length of intensive care unit stay was shorter in the PPLI group (20.01 [n=36] vs. 28.10 [n=5] days) (P=0.132). Conclusions: Targeted PPLI administration to the carotid bulb decreased aberrant heart rates and blood pressure changes induced by carotid stent deployment and balloon inflation. As CBR sensitivity increases with decreasing distance to the stenotic lesion from the CCA bifurcation, PPLIs may help stabilize patients during procedures for stenotic lesions closer to the CCA.

9.
Adv Mater ; 35(37): e2203352, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35723973

RESUMO

The fields of brain-inspired computing, robotics, and, more broadly, artificial intelligence (AI) seek to implement knowledge gleaned from the natural world into human-designed electronics and machines. In this review, the opportunities presented by complex oxides, a class of electronic ceramic materials whose properties can be elegantly tuned by doping, electron interactions, and a variety of external stimuli near room temperature, are discussed. The review begins with a discussion of natural intelligence at the elementary level in the nervous system, followed by collective intelligence and learning at the animal colony level mediated by social interactions. An important aspect highlighted is the vast spatial and temporal scales involved in learning and memory. The focus then turns to collective phenomena, such as metal-to-insulator transitions (MITs), ferroelectricity, and related examples, to highlight recent demonstrations of artificial neurons, synapses, and circuits and their learning. First-principles theoretical treatments of the electronic structure, and in situ synchrotron spectroscopy of operating devices are then discussed. The implementation of the experimental characteristics into neural networks and algorithm design is then revewed. Finally, outstanding materials challenges that require a microscopic understanding of the physical mechanisms, which will be essential for advancing the frontiers of neuromorphic computing, are highlighted.

10.
Sci Adv ; 9(11): eade4838, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36930716

RESUMO

The cointegration of artificial neuronal and synaptic devices with homotypic materials and structures can greatly simplify the fabrication of neuromorphic hardware. We demonstrate experimental realization of vanadium dioxide (VO2) artificial neurons and synapses on the same substrate through selective area carrier doping. By locally configuring pairs of catalytic and inert electrodes that enable nanoscale control over carrier density, volatility or nonvolatility can be appropriately assigned to each two-terminal Mott memory device per lithographic design, and both neuron- and synapse-like devices are successfully integrated on a single chip. Feedforward excitation and inhibition neural motifs are demonstrated at hardware level, followed by simulation of network-level handwritten digit and fashion product recognition tasks with experimental characteristics. Spatially selective electron doping opens up previously unidentified avenues for integration of emerging correlated semiconductors in electronic device technologies.

11.
Respir Care ; 57(5): 758-63, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22152429

RESUMO

BACKGROUND: The functional role of the human diffuse panbronchiolitis critical region 1 (DPCR1) gene, located in the major histocompatibility complex class I, has not been widely investigated. However, this gene is a well known genetic marker for diffuse panbronchiolitis, a disease affecting human respiratory bronchioles. In this study we explored the association between polymorphisms in DPCR1 and aspirin-exacerbated respiratory disease (AERD), an asthma phenotype. METHODS: Genotyping of 6 polymorphisms was carried out in a total of 189 Korean asthmatic patients stratified into 93 AERD cases and 96 aspirin tolerant asthma controls. Subjects who exhibited significant decrease of FEV(1) by aspirin provocation were identified as AERD subjects. Logistic and regression analyses were performed to investigate the association between DPCR1 polymorphisms and the risk of AERD as well as FEV(1) decline. RESULTS: Initial analysis revealed significant association of rs2517449 with AERD, with a P value of .03 via a recessive model; however, the association signal disappeared after multiple testing corrections. In addition, rs2517449 and rs2240804 also showed association signals with decline of FEV(1) after aspirin provocation (P = .007 and .03, respectively, in a recessive model). After testing for multiple comparisons, only the association signal from rs2517449 was retained (P(corr) = .04), while other polymorphisms showed no associations with the risk of AERD and FEV(1) decline. CONCLUSIONS: Our results show that polymorphisms in DPCR1 are not associated with the risk of AERD.


Assuntos
Povo Asiático/genética , Asma Induzida por Aspirina/genética , Polimorfismo Genético/genética , Proteínas/genética , Adolescente , Adulto , Idoso , Asma Induzida por Aspirina/etnologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas , República da Coreia , Adulto Jovem
12.
J Korean Med Sci ; 27(4): 343-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22468095

RESUMO

Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyposis and aspirin hypersensitivity. The aspirin-induced bronchospasm is mediated by mast cell and eosinophilic inflammation. Recently, it has been reported that the expression of discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is up-regulated in lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a component of activator protein-2 (AP-2) that is known to regulate IL-8 production in human lung fibroblasts and epithelial cells. To investigate the associations between AERD and DCBLD2 polymorphisms, 12 common variants were genotyped in 163 AERD subjects and 429 aspirin tolerant asthma (ATA) controls. Among these variants, seven SNPs (rs1371687, rs7615856, rs828621, rs828618, rs828616, rs1062196, and rs8833) and one haplotype (DCBLD2-ht1) show associations with susceptibility to AERD. In further analysis, this study reveals significant associations between the SNPs or haplotypes and the percentage of forced expiratory volume in one second (FEV(1)) decline following aspirin challenge using multiple linear regression analysis. Furthermore, a non-synonymous SNP rs16840208 (Asp723Asn) shows a strong association with FEV(1) decline in AERD patients. Although further studies for the non-synonymous Asp723Asn variation are needed, our findings suggest that DCBLD2 could be related to FEV(1)-related phenotypes in asthmatics.


Assuntos
Povo Asiático/genética , Aspirina/efeitos adversos , Asma Induzida por Aspirina/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Alelos , Asma Induzida por Aspirina/etiologia , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Volume Expiratório Forçado/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , República da Coreia , Fatores de Risco , Adulto Jovem
13.
Science ; 375(6580): 533-539, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-35113713

RESUMO

Reconfigurable devices offer the ability to program electronic circuits on demand. In this work, we demonstrated on-demand creation of artificial neurons, synapses, and memory capacitors in post-fabricated perovskite NdNiO3 devices that can be simply reconfigured for a specific purpose by single-shot electric pulses. The sensitivity of electronic properties of perovskite nickelates to the local distribution of hydrogen ions enabled these results. With experimental data from our memory capacitors, simulation results of a reservoir computing framework showed excellent performance for tasks such as digit recognition and classification of electrocardiogram heartbeat activity. Using our reconfigurable artificial neurons and synapses, simulated dynamic networks outperformed static networks for incremental learning scenarios. The ability to fashion the building blocks of brain-inspired computers on demand opens up new directions in adaptive networks.

14.
Biophys J ; 101(5): 1193-201, 2011 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-21889457

RESUMO

Lactophoricin (LPcin-I) is an antimicrobial, amphiphatic, cationic peptide with 23-amino acid residues isolated from bovine milk. Its analogous peptide, LPcin-II, lacks six N-terminal amino acids compared to LPcin-I. Interestingly, LPcin-II does not display any antimicrobial activity, whereas LPcin-I inhibits the growth of both Gram-negative and Gram-positive bacteria without exhibiting any hemolytic activity. Uniformly (15)N-labeled LPcin peptides were prepared by the recombinant expression of fusion proteins in Escherichia coli, and their properties were characterized by electrospray ionization mass spectrometry, circular dichroism spectroscopy, and antimicrobial activity tests. To understand the structure-activity relationship of these two peptides, they were studied in model membrane environments by a combination of solution and solid-state NMR spectroscopy. We determined the tertiary structure of LPcin-I and LPcin-II in the presence of dodecylphosphorylcholine micelles by solution NMR spectroscopy. Magnetically aligned unflipped bicelle samples were used to investigate the structure and topology of LPcin-I and LPcin-II by solid-state NMR spectroscopy.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Ressonância Magnética Nuclear Biomolecular , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias/efeitos dos fármacos , Bovinos , Dicroísmo Circular , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Estrutura Secundária de Proteína , Soluções , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade
15.
Immunogenetics ; 63(1): 13-21, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21086123

RESUMO

Aspirin-intolerant asthma (AIA) is an asthma phenotype characterized by the development of bronchoconstriction following ingestion of aspirin. Despite the well-defined pathological trigger, the underlying mechanisms of AIA are still unclear. With the biophysical characteristics of the human EMI domain-containing protein 2 (EMID2) gene in relation to the extracellular matrix deposition and epithelial-mesenchymal transition as pivotal characteristics of airway remodeling in asthma, we hypothesized that genetic polymorphisms of EMID2 might affect the development of AIA. In this study, the allelic associations of 49 single-nucleotide polymorphisms (SNPs) of the human EMID2 gene were evaluated from 163 AIA patients and 429 aspirin-tolerant asthma (ATA) subjects as controls in a Korean population. Logistic analysis showed that five SNPs (P = 0.01-0.04, but P (corr) > 0.05) and EMID2_BL2_ht2 haplotype (unique to the minor alleles of rs4727494 and rs13233066; P = 0.02; P (corr) = 0.02) were significantly associated with AIA. More interestingly, regression analysis of the decline of forced expiratory volume in one second (FEV(1)) by aspirin provocation revealed that 10 SNPs (P = 0.003-0.04) and four relevant haplotypes (P = 0.002-0.02) were significantly associated with the fall rate of FEV(1) by aspirin provocation, indicating that genetic polymorphisms of EMID2 could cause meaningful deficits in the upper and lower airways among AIA patients. These findings provide evidence that EMID2 may be a susceptible genetic factor for aspirin hypersensitivity among asthmatics in Korean population.


Assuntos
Aspirina/efeitos adversos , Asma/complicações , Asma/genética , Colágeno/genética , Hipersensibilidade a Drogas/complicações , Hipersensibilidade a Drogas/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Mapeamento Cromossômico , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , República da Coreia , Adulto Jovem
16.
J Med Virol ; 83(11): 1892-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21915862

RESUMO

The RecA homolog, E. coli (S. cerevisiae) (RAD51) may modulate hepatitis B virus (HBV) infection by maintaining genome integrity and mediating homologous DNA repairs. In this study, 16 sequence variations were detected by resequencing all exons, the exon-intron boundary, and promoter regions of the human RAD51 gene in DNA samples of 24 unrelated individuals. To investigate the association of common variations in the RAD51 locus with HBV infection and hepatocellular carcinoma (HCC) occurrence, six common polymorphisms were genotyped in a total of 1,103 Korean HBV cohort, composed of 433 spontaneously recovered patients as controls and 670 chronic carriers of HBV, who were stratified further into 327 cirrhosis/chronic hepatitis patients and 343 patients with HCC infected with HBV. Logistic analyses revealed no significant association of RAD51 polymorphisms and haplotypes with HBV clearance and HCC occurrence (P > 0.05). Furthermore, with age of infection as an important factor in disease progression to HCC, results from the Cox proportional hazards analysis showed no significant associations between any of the tested RAD51 variants and the age of onset of HCC (P > 0.05), suggesting that genetic polymorphisms of RAD51 may not play an important role in clearance of HBV and disease progression to HCC. Although studies in other populations are needed to confirm these findings, this preliminary data may contribute to the current knowledge on the pathogenesis of hepatitis.


Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Hepatite B/genética , Polimorfismo de Nucleotídeo Único , Rad51 Recombinase/genética , Adulto , Idoso , Povo Asiático , Estudos de Coortes , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade
17.
Int Arch Allergy Immunol ; 155(4): 395-402, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21346370

RESUMO

BACKGROUND: Aspirin-intolerant asthma (AIA) is a clinical syndrome characterized by acute bronchoconstriction following the ingestion of aspirin. Solute carrier family 22, member 2 (SLC22A2), also known as organic cation transporter 2 (OCT2), is predominantly expressed in the luminal membrane of airway epithelial cells and has been shown to mediate the transport of prostaglandins on the cyclooxygenase pathway which is regulated by aspirin blockage. Recently, SLC22A2-mediated uptake inhibition by several nonsteroidal anti-inflammatory drugs and decreased SLC22A2 transport activity by its genetic variants have been elucidated in asthma. METHODS: To investigate the associations between AIA and genetic polymorphisms of the SLC22A2 gene, 18 variants were genotyped in 163 AIA subjects and 429 aspirin-tolerant asthma (ATA) controls. Logistic analyses were used to evaluate p values for the associations of SLC22A2 polymorphisms with AIA. RESULTS: One common polymorphism in intron 5, i.e. rs316021, was significantly associated with susceptibility to AIA (p = 0.004, P(corr) = 0.05, OR = 0.60, 95% CI = 0.43-0.85 in a codominant model). The minor allele frequency of rs316021 in the AIA group was significantly lower than that in the ATA controls. In addition, a polymorphism in intron 4 (rs3912161) and a haplotype (SLC22A2-ht3) showed significantly stronger association signals with the FEV(1) fall rate induced by aspirin provocation in AIA subjects compared with ATA controls (p = 0.004, P(corr) = 0.05). CONCLUSION: Our findings suggest that SLC22A2 could be a susceptibility gene for aspirin intolerance in asthmatics.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Asma Induzida por Aspirina/genética , Predisposição Genética para Doença , Proteínas de Transporte de Cátions Orgânicos/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Transportador 2 de Cátion Orgânico , Adulto Jovem
18.
Pulm Pharmacol Ther ; 24(5): 595-601, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21624492

RESUMO

The angiotensinogen (AGT) gene enhances the effect of several bronchoconstrictors and produces a peptide that is accumulated in the airways of asthma patients; events that may underpin the pathogenesis of aspirin-intolerant asthma (AIA). To carry out a case-control analysis between AGT and aspirin-induced bronchospasm following treatment with an anti-asthma drug, montelukast (MLK), 38 single nucleotide polymorphisms (SNPs) in AGT were genotyped in 56 AIA cohort. Genotyping was performed with TaqMan assay and haplotypes were inferred using PHASE algorithm ver. 2.0. Statistical analyses of each SNPs and haplotypes were performed using SAS version 9.1. Among 13 variants displaying significant signals, two SNPs (+2401C>G and +2476C>T) in the intronic region of AGT were significantly associated with modification of drug response even after correction for multiple testing (P=0.0009-0.002; P(corr)=0.02-0.03). Furthermore, the two variants also exhibited associations with MLK response rate (P=0.0003-0.0006; P(corr)=0.006-0.01). Although our results are preliminary and further replication in a larger-scale group of subjects should be warranted, these observations provide evidence that AGT variants might be one of genetic factors involved in the response of anti-asthma drugs in AIA patients.


Assuntos
Acetatos/farmacologia , Angiotensinogênio/genética , Antiasmáticos/farmacologia , Asma Induzida por Aspirina/genética , Quinolinas/farmacologia , Adolescente , Adulto , Idoso , Algoritmos , Povo Asiático/genética , Aspirina/efeitos adversos , Aspirina/imunologia , Asma Induzida por Aspirina/tratamento farmacológico , Espasmo Brônquico/induzido quimicamente , Estudos de Casos e Controles , Ciclopropanos , Hipersensibilidade a Drogas/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , República da Coreia , Sulfetos , Adulto Jovem
19.
J Asthma ; 48(6): 539-45, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21726122

RESUMO

BACKGROUND: Exacerbation of asthma symptoms due to aspirin ingestion may lead to life-threatening lung failure. The adhesion molecule CD58 gene may play a crucial role in aspirin-exacerbated respiratory disease (AERD) pathogenesis by mediating the biological functions of asthma-inducing mechanisms including T helper cells, proinflammatory cytokines, and natural killer T cells. OBJECTIVE: This study aimed to investigate the association of CD58 variations with aspirin-induced bronchospasm in Korean asthma patients. METHODS: Seven single-nucleotide polymorphisms were selected for genotyping based on previously reported polymorphisms in the International HapMap database. Genotyping was carried out using TaqMan assay and 2 major haplotypes were obtained in 163 AERD cases and 429 aspirin-tolerant asthma controls. Frequency distributions of CD58 variations were analyzed using logistic and regression models. RESULTS: Results showed that none of the analyzed CD58 single-nucleotide polymorphisms and haplotypes was significantly associated with AERD development and fall rate of FEV(1) by aspirin provocation, an important diagnostic marker of aspirin hypersensitivity. CONCLUSIONS: This preliminary study suggests that CD58 does not affect AERD susceptibility in a Korean population, and may provide a new direction for future disease etiology.


Assuntos
Povo Asiático/genética , Asma Induzida por Aspirina/genética , Antígenos CD58/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Aspirina/farmacologia , Asma Induzida por Aspirina/complicações , Asma Induzida por Aspirina/fisiopatologia , Índice de Massa Corporal , Testes de Provocação Brônquica , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Volume Expiratório Forçado/fisiologia , Frequência do Gene/genética , Haplótipos/genética , Humanos , Íntrons/genética , Masculino , Cloreto de Metacolina/farmacologia , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Regiões Promotoras Genéticas/genética , República da Coreia , Fumar/epidemiologia , Adulto Jovem
20.
Dig Dis Sci ; 56(9): 2735-41, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21380615

RESUMO

BACKGROUND: The complement component 9 (C9), a major cytolytic protein in the complement system, plays an important role in the immunological process. However, associations between genetic variations of the complement factor and chronic hepatitis B virus infection still need to be investigated. AIMS: We hypothesized that genetic variations in the complement component 9 gene can influence the clearance of chronic hepatitis B virus infection, hepatocellular carcinoma occurrence, and onset age of hepatocellular carcinoma. To investigate the relationship between complement component 9 variations and these disease phenotypes, we performed a case-control association analysis in a Korean population. METHODS: Genetic variations were identified through direct DNA sequencing and genotyped using TaqMan assay (n = 1,103). In order to investigate the relationship of complement component 9 with chronic hepatitis B virus clearance and hepatocellular carcinoma occurrence, differences in SNP and haplotype frequency distributions were analyzed using logistic and multiple regression analyses with adjusted age and gender as covariates. RESULTS: Although +23189C>T polymorphism in exon 4 and C9_ht2 [T-G-C-A-C] were significantly associated with clearance of chronic hepatitis B virus infection and hepatocellular carcinoma occurrence, the association signals were not retained after multiple testing corrections. CONCLUSIONS: We conclude that variations in the complement component 9 gene are unlikely to influence clearance of chronic hepatitis B virus infection and hepatocellular carcinoma occurrence. Although this preliminary result provides meaningful information, further functional investigations in other genetic factors for pathway analyses are required.


Assuntos
Complemento C9/genética , Predisposição Genética para Doença , Hepatite B/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
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