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1.
Arch Gerontol Geriatr ; 91: 104243, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32916429

RESUMO

OBJECTIVES: The aim of this study was to determine whether age at menopause is associated with physical frailty. METHODS: This was a cross-sectional study that included 1264 women (70-84 years) from the Korean and Aging Cohort Study (KFACS) who had records of their ages at menarche and their ages at menopause and had experienced a natural menopause. We used Fried criteria to assess physical frailty status. The ages at menopause and menarche were collected using self-reported questionnaires. RESULTS: The prevalence of physical frailty decreased by 5.3 % with each year of increase in age at menopause after adjusting for age, marital status, years of education, diabetes mellitus, hypertension, polypharmacy, hospitalizations, falls, and hormone replacement therapy (p = 0.005). The prevalence of frailty significantly decreased by 4.1 % when the reproductive span increased by a year (p = 0.019). CONCLUSIONS: This study found that a later menopausal age was associated with a lower risk of frailty using Fried criteria. In addition, it showed that a longer reproductive span was associated with a lower prevalence of frailty.

2.
Br J Anaesth ; 123(2): e424-e433, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31056241

RESUMO

Complex regional pain syndrome (CRPS) is a life-altering condition that usually affects the extremities after a trauma or nerve injury. The physiologic changes that occur as a result of the inciting injury are complex, as the name of the syndrome implies. The pain and disability associated with CRPS often lead to psychological co-morbidities that create a vicious cycle of pain, isolation, and depression. We review recent developments in the understanding of CRPS and advancements in management of this syndrome. Further research in targeting specific mechanisms involved in the pathophysiology of CRPS should lead to prevention of this condition.


Assuntos
Síndromes da Dor Regional Complexa/fisiopatologia , Síndromes da Dor Regional Complexa/terapia , Síndromes da Dor Regional Complexa/diagnóstico , Humanos
3.
Ann Oncol ; 30(7): 1104-1113, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30977778

RESUMO

BACKGROUND: Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade. PATIENTS AND METHODS: We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD. RESULTS: A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival [hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868-7.440] and overall survival (HR, 5.079; 95% CI, 3.136-8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7-CD45RA- T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate. CONCLUSION: HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Metástase Linfática , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Carga Tumoral
4.
J Colloid Interface Sci ; 534: 350-356, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30243176

RESUMO

The development of efficient and earth-abundant electrocatalysts for overall water splitting is important but still challenging. Herein, iron phosphate (FePi) electrode is synthesized using a successive ionic layer deposition and reaction (SILAR) method on a nickel foam substrate at room temperature and is used as a bifunctional electrocatalyst for water splitting. The prepared FePi electrodes show excellent electrocatalytic activity and stability for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). The FePi electrode exhibits low overpotential of 230 mV and 157 mV towards the OER and HER, respectively, with superior long-term stability. As a result, an electrolyzer that exploits FePi as both the anode and the cathode is constructed, which requires a cell potential of 1.67 V to deliver a 10 mA cm-2 current density in 1 M KOH solution. The exceptional features of the catalyst lie in its structure and active metal sites, increasing surface area, accelerated electron transport and promoted reaction kinetics. This study may provide a facile and scalable approach to design a high-efficiency, earth-abundant electrocatalyst for water splitting.

5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 5150-5153, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30441499

RESUMO

Magnetic resonance (MR) simulators have recently gained popularity; it avoids the unnecessary radiation exposure associated with Computed Tomography (CT) when used for radiation therapy planning. We propose a method for pseudo CT estimation from MR images based on joint dictionary learning. Patient-specific anatomical features were extracted from the aligned training images and adopted as signatures for each voxel. The most relevant and informative features were identified to train the joint dictionary learning-based model. The well-trained dictionary was used to predict the pseudo CT of a new patient. This prediction technique was validated with a clinical study of 12 patients with MR and CT images of the brain. The mean absolute error (MAE), peak signal-to-noise ratio (PSNR), normalized cross correlation (NCC) indexes were used to quantify the prediction accuracy. We compared our proposed method with a state-of-the-art dictionary learning method. Overall our proposed method significantly improves the prediction accuracy over the state-of-the-art dictionary learning method. We have investigated a novel joint dictionary Iearning- based approach to predict CT images from routine MRIs and demonstrated its reliability. This CT prediction technique could be a useful tool for MRI-based radiation treatment planning or attenuation correction for quantifying PET images for PET/MR imaging.


Assuntos
Tomografia Computadorizada por Raios X , Encéfalo , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Reprodutibilidade dos Testes
6.
Ann Oncol ; 28(6): 1250-1259, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28460066

RESUMO

BACKGROUND: We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). METHODS: The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling. RESULTS: The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations of FGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib. CONCLUSIONS: FGFR gene expression signatures are predictors for the response to dovitinib in LSCC.


Assuntos
Benzimidazóis/uso terapêutico , Biomarcadores/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Ensaios Clínicos como Assunto , Neoplasias Pulmonares/tratamento farmacológico , Quinolonas/uso terapêutico , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Carcinoma de Células Escamosas/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Sequenciamento do Exoma
8.
Clin Otolaryngol ; 42(3): 687-692, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27886463

RESUMO

BACKGROUND: Although many factors have been found to be involved in recovery from Bell's palsy, no study has investigated the association between recovery from Bell's palsy and obesity. This study therefore evaluated the association between recovery from Bell's palsy and body mass index (BMI). METHODS: Subjects were classified into five groups based on BMI (kg/m2 ). Demographic and clinical characteristics were compared among these groups. Assessed factors included sex, age, time from paralysis to visiting a hospital, the presence of comorbidities such as diabetes mellitus and hypertension, degree of initial facial nerve paralysis by House-Brackmann (H-B) grade and neurophysiological testing, and final recovery rate. RESULTS: Based on BMI, 37 subjects were classified as underweight, 169 as normal weight, 140 as overweight, 155 as obese and 42 as severely obese. Classification of the degree of initial facial nerve paralysis as moderate or severe, according to H-B grade and electroneurography, showed no difference in severity of initial facial paralysis among the five groups (P > 0.05). However, the final recovery rate was significantly higher in the normal weight than in the underweight or obese group (P < 0.05). CONCLUSIONS: Obesity or underweight had no effect on the severity of initial facial paralysis, but the final recovery rate was lower in the obese and underweight groups than in the normal group.


Assuntos
Paralisia de Bell/fisiopatologia , Índice de Massa Corporal , Expressão Facial , Paralisia Facial/fisiopatologia , Obesidade/complicações , Recuperação de Função Fisiológica , Idoso , Paralisia de Bell/complicações , Paralisia Facial/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Estudos Retrospectivos
9.
Heredity (Edinb) ; 117(6): 393-399, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27649621

RESUMO

Many features of virus populations make them excellent candidates for population genetic study, including a very high rate of mutation, high levels of nucleotide diversity, exceptionally large census population sizes, and frequent positive selection. However, these attributes also mean that special care must be taken in population genetic inference. For example, highly skewed offspring distributions, frequent and severe population bottleneck events associated with infection and compartmentalization, and strong purifying selection all affect the distribution of genetic variation but are often not taken into account. Here, we draw particular attention to multiple-merger coalescent events and background selection, discuss potential misinference associated with these processes, and highlight potential avenues for better incorporating them into future population genetic analyses.


Assuntos
Genética Populacional , Seleção Genética , Vírus/genética , Evolução Biológica , Ligação Genética , Modelos Genéticos , Taxa de Mutação
10.
Cell Death Differ ; 22(8): 1341-52, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25591736

RESUMO

Lung cancer is the number one cancer killer, and metastasis is the main cause of high mortality in lung cancer patients. However, mechanisms underlying the development of lung cancer metastasis remain unknown. Using genome-wide transcriptional analysis in an experimental metastasis model, we identified laminin γ2 (LAMC2), an epithelial basement membrane protein, to be significantly upregulated in lung adenocarcinoma metastatic cells. Elevated LAMC2 increased traction force, migration, and invasion of lung adenocarcinoma cells accompanied by the induction of epithelial-mesenchymal transition (EMT). LAMC2 knockdown decreased traction force, migration, and invasion accompanied by EMT reduction in vitro, and attenuated metastasis in mice. LAMC2 promoted migration and invasion via EMT that was integrin ß1- and ZEB1-dependent. High LAMC2 was significantly correlated with the mesenchymal marker vimentin expression in lung adenocarcinomas, and with higher risk of recurrence or death in patients with lung adenocarcinoma. We suggest that LAMC2 promotes metastasis in lung adenocarcinoma via EMT and may be a potential therapeutic target.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Laminina/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Humanos , Laminina/genética , Camundongos
11.
Opt Express ; 22(23): 29037-47, 2014 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-25402143

RESUMO

We report a practical 12.5-Gb/s, 12.5-GHz-spaced ultra-dense wavelength-division-multiplexed passive optical network (UD-WDM PON). For the cost-effectiveness, we implement the downstream links by using electro-absorption modulated lasers (EMLs) in the 4-level pulse amplitude modulation (4PAM) format and PIN receivers, and the upstream links by using reflective semiconductor optical amplifiers (RSOAs) modulated in the quadrature phase-shift-keying (QPSK) format and low-cost self-homodyne receivers. To further enhance its cost-effectiveness, we also utilize an optical frequency comb generator, instead of a large number of wavelength-selected lasers, to provide the seed light for these colorless RSOAs. We optimize the operating conditions of the EMLs and RSOAs to maximize the power margins in the presence of the crosstalk arising from closely spaced neighboring channels and the inter-symbol interference (ISI) caused by the narrow passband of the cascaded arrayed-waveguide gratings (AWGs) as well as the limited modulation bandwidths of RSOAs. The experimental results show that we can secure the power margins of >2.5 dB for both upstream and downstream links of the proposed UD-WDM PON.


Assuntos
Amplificadores Eletrônicos , Tecnologia de Fibra Óptica/instrumentação , Dispositivos Ópticos , Semicondutores , Processamento de Sinais Assistido por Computador/instrumentação , Telecomunicações/instrumentação , Desenho de Equipamento
12.
Curr Med Chem ; 21(20): 2266-75, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24533810

RESUMO

Over the last centuries, there were many important discoveries in medicine that were crucial for gaining a better understanding of several physiological processes. Molecular modelling techniques are powerful tools that have been successfully used to analyse and interface medicinal chemistry studies with electrochemical experimental results. This special combination can help to comprehend medicinal chemistry problems, such as predicting biological activity and understanding drug action mechanisms. Electrochemistry has provided better comprehension of biological reactions and, as a result of many technological improvements, the combination of electrochemical techniques and biosensors has become an appealing choice for pharmaceutical and biomedical analyses. Therefore, this review will briefly outline the present scope and future advances related to the integration of electrochemical and medicinal chemistry approaches based on various applications from recent studies.


Assuntos
Química Farmacêutica , Biologia Computacional , Técnicas Eletroquímicas , Animais , Desenho de Fármacos , Humanos , Ligantes , Relação Quantitativa Estrutura-Atividade
13.
Dis Esophagus ; 27(8): 798-801, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24152165

RESUMO

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteínas de Membrana Transportadoras/genética , Fosfoinositídeo Fosfolipase C/genética , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Carcinoma de Células Escamosas do Esôfago , Feminino , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , República da Coreia , Risco
14.
Plant Dis ; 98(2): 275, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30708749

RESUMO

In December 2012, symptoms of typical bacterial leaf blight were observed on carrot plants (Daucus carota L. subsp. sativus) cultivated in commercial fields in Kujwa, Jeju, Korea. The disease was detected in 40% of 50 fields surveyed with an incidence of 10% on average. The bacterial leaf blight lesions on leaf blades were elongated, dark brown to black with water-soaked edges and chlorotic halos. Lesions were also crescent-shaped to V-shaped on leaflets. Four bacterial isolates were recovered on trypticase soy agar from leaf lesions that were surface-sterilized in 70% ethyl alcohol for 20 s. Identity of the isolates was confirmed by PCR product (1,266-bp) using a specific primer set for Xanthomonas hortorum pv. carotae (Kendrick 1934) Vauterin et al. 1995, XhcPP03 (1). All isolates were gram-negative, aerobic rods with a single polar flagellum. Isolates were positive for catalase and negative for oxidase. In phenotypic tests for differentiation of Xanthomonas (2), the isolates positive for mucoid growth on yeast extract-dextrose-calcium carbonate agar, growth at 35°C, hydrolysis of esculin, protein digestion, alkaline in litmus milk, acid production from arabitol, and utilization of glycerol and melibiose. The isolates were negative for growth on SX medium, hydrolysis of starch, and ice nucleation. The gyrB gene (863 bp) and the rpoD gene (870 bp) were sequenced to aid identification of the original isolates using published PCR primer sets, Xgyr1BF/Xgyr1BR and XrpoD1F/XrpoD1R (4), respectively. Sequences of the gyrB gene (GenBank accessions KC920729 to KC920732) from the carrot isolates shared 100% sequence identity with that of the X. hortorum pv. carotae strain NCPPB 425 (EU285243). In phylogenetic analyses based on the partial sequences of the gyrB and the rpoD genes for Xanthomonas spp. available at NCBI (4), and sequences of the carrot isolates (KC920734 to KC920737 for rpoD gene) using the Neighbor-joining method in MEGA Version 5.1 (3), the isolates were clustered in the X. hortorum-cynarae-garnderi group. Pathogenicity of the isolates was tested by spray inoculation with a bacterial suspension (106 CFU/ml) prepared in sterile distilled water at 6 to 7 true-leaf stage (three plants per isolate). Sterile distilled water was used as negative control. The inoculated plants were incubated in a growth chamber (25°C and 95% relative humidity [RH]) for 15 hr, and then transferred to a greenhouse at 24 to 28°C and 65% RH. Characteristic leaf blight symptoms developed on inoculated carrot plants, while no symptoms were observed on the negative control plants 14 days after inoculation. The bacterium was re-isolated from symptomatic tissue and the identity confirmed through gyrB gene sequence analysis (4). Based on PCR, morphological and phenotypic tests, sequence analysis, and pathogenicity assays, the isolates were identified as X. hortorum pv. carotae. To our knowledge, this is the first report of bacterial leaf blight of carrot caused by X. hortorum pv. carotae in Korea. The detection of this pathogen could have a significant economic impact due to yield losses from disease development. Consolidation of quarantine inspection on imported carrot seeds needs to control an outbreak of the disease. Crop rotation and plowing are recommended to reduce incidence of the disease in the infested fields. References: (1) J. A. Kimbrel et al. Mol. Plant Pathol. 12:580, 2011. (2) N. W. Schaad et al. Page 189 in: Laboratory Guide for Identification of Plant Pathogenic Bacteria. 3rd ed. N. W. Schaad et al., eds. The American Phytopathological Society, St. Paul, MN, 2001. (3) K. Tamura et al. Mol. Biol. Evol. 28:2731, 2011. (4) J. M. Young et al. Syst. Appl. Microbiol. 31:366, 2008.

15.
Ann Oncol ; 24(9): 2364-70, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23788756

RESUMO

BACKGROUND: To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma. PATIENTS AND METHODS: We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization. RESULTS: Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01). CONCLUSIONS: The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Recombinantes de Fusão/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Adulto , Idoso , Quinase do Linfoma Anaplásico , Antígenos de Diferenciação de Linfócitos B/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Crizotinibe , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Gefitinibe , Frequência do Gene/genética , Rearranjo Gênico/genética , Glutamatos/farmacologia , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Guanina/farmacologia , Guanina/uso terapêutico , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação/genética , Pemetrexede , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas p21(ras) , Pirazóis/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Quinazolinas/farmacologia , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fumar , Resultado do Tratamento , Proteínas ras/genética
16.
Oncogene ; 32(48): 5449-57, 2013 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-23644659

RESUMO

It has been suggested that clec14a may be involved in tumor angiogenesis. However, a molecular mechanism has not been clearly identified. In this study, we show for the first time that C-type lectin-like domain (CTLD) of clec14a may be important for regulating cell migration and filopodia formation. Using phage display technology, recombinant human antibodies specific to the CTLDs of human and mouse clec14a (clec14a-CTLD (immunoglobulin G) IgG) were selected. Functional assays using the antibodies showed that clec14a-CTLD IgGs specifically blocked endothelial cell migration and tube formation without affecting cell viability or activation. Further, clec14a-CTLD IgGs inhibited clec14a-mediated cell-cell contact by blocking interaction between CTLDs. Finally, clec14a cross-linking by the clec14a-CTLD IgGs significantly downregulated clec14a expression on the surface of endothelial cells. These results strongly suggest that the clec14a-CTLD may be a key domain in angiogenesis, and that clec14a-CTLD IgGs specifically inhibit angiogenesis by modulating CTLD-mediated cell interactions and clec14a expression on the surface of endothelial cells.


Assuntos
Moléculas de Adesão Celular/química , Moléculas de Adesão Celular/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Imunoglobulina G/imunologia , Lectinas Tipo C/química , Lectinas Tipo C/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Neovascularização Patológica/metabolismo , Animais , Especificidade de Anticorpos , Biomarcadores Tumorais/química , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Moléculas de Adesão Celular/antagonistas & inibidores , Moléculas de Adesão Celular/imunologia , Comunicação Celular , Movimento Celular , Sobrevivência Celular , Regulação para Baixo , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Imunoglobulina G/química , Lectinas Tipo C/antagonistas & inibidores , Lectinas Tipo C/imunologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/imunologia , Camundongos , Estrutura Terciária de Proteína , Pseudópodes/metabolismo , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/imunologia
17.
Opt Express ; 21(3): 3721-5, 2013 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-23481828

RESUMO

We demonstrate the 40-Gb/s upstream transmission in the 60-km reach wavelength-division-multiplexed passive optical network (WDM PON) implemented by using directly modulated reflective semiconductor optical amplifiers (RSOAs) and self-homodyne receivers. It is difficult to operate the RSOA at 40 Gb/s due to its limited modulation bandwidth. To overcome this problem and generate 40-Gb/s upstream signal, we utilize the quadrature phase-shift-keying (QPSK) format and the offset polarization-division-multiplexing (PDM) technique. For this purpose, we install two RSOAs at each ONU and provide the seed light for these RSOAs by polarization-multiplexing the outputs of two lasers with a small frequency offset (20 GHz). This frequency offset is used to separate the polarization-multiplexed seed light by using a simple delay-line interferometer (DLI), instead of the polarization-beam splitter and polarization controller, at the ONU. The separated seed light is modulated by each RSOA at 20 Gb/s in the QPSK format, and then combined again by the DLI before sent back to the central office (CO). The results show that this WDM PON can support the transmission of 40-Gb/s channels spaced at 50 GHz over 60 km without using any remote optical amplifiers.


Assuntos
Amplificadores Eletrônicos , Tecnologia de Fibra Óptica/instrumentação , Dispositivos Ópticos , Semicondutores , Processamento de Sinais Assistido por Computador/instrumentação , Telecomunicações/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento
19.
Cytopathology ; 24(2): 99-104, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22612864

RESUMO

OBJECTIVE: ThinPrep (TP), one of the Food and Drug Administration-approved liquid-based cytology (LBC) preparations, is widely used for gynaecological and non-gynaecological cytology samples. A unique physical artefact caused by the compression at the periphery in TP slides has not been adequately evaluated to date. METHODS: We processed four established tumour cell lines (MKN28, MKN45, KG-1 and NB4) and mononuclear cells isolated from whole blood over Ficoll-Plaque for TP preparations. For this part of the study, we included five normal cervical LBC preparations. We then auto-counted and auto-measured the area, mean grey value and Feret's diameter in both the inner disc and peripheral rim of the preparations by image morphometry. In addition, we compared the distribution of atypical cell groups in the peripheral rim and inner disc of 132 lung aspirates, 80 thyroid aspirates, 212 cerebrospinal fluids (CSFs) and 50 gynaecological samples. RESULTS: The areas and Feret's diameters of the cytoplasm in the peripheral compressed rim area were statistically larger than those of cells in the inner disc. The mean grey values of cells (cytoplasm and nucleus) in the peripheral compression rim were also smaller than those in the inner disc cells, leading to decreases in nuclear and cytoplasmic chromatism. Except for the mean grey values, the differences were not significant in the cervical samples. CONCLUSIONS: Cellular morphology may be markedly distorted in the peripheral rim, regardless of cell malignancy, which may lead to the misinterpretation of cells during the screening. Accordingly, cytological diagnosis based on the findings within the peripheral rim should take this phenomenon into account. Compressed cells found in the peripheral rim should be interpreted with caution when TP slides are used for cytopathological diagnosis.


Assuntos
Biópsia por Agulha Fina/métodos , Citodiagnóstico/métodos , Processamento de Imagem Assistida por Computador/métodos , Linhagem Celular Tumoral , Colo do Útero/patologia , Feminino , Humanos , Pulmão/patologia , Masculino , Gravidez , Glândula Tireoide/patologia , Esfregaço Vaginal
20.
Plant Dis ; 97(10): 1376, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30722163

RESUMO

In August 2011, bacterial leaf spot was observed on witloof (Cichorium intybus L. var. foliosum) grown in a commercial field with 15% incidence in Injae, Korea. Symptoms on leaves included irregular brown to reddish brown spots in the center. Bacterial streaming from the lesions was observed microscopically. Bacterial isolates (BC3286, BC3287, and BC3308-BC3310) were recovered on Trypticase soy agar from lesions surface-sterilized in 70% ethyl alcohol for 30 s. The isolates were gram negative, urease negative, fluorescent on King's B agar, and had aerobic rods with 2 to 6 polar flagella. Pathogenicity tests were separately performed in different greenhouses located in Suwon (National Academy of Agricultural Science) and Chuncheon (Gangwondo Agricultural Research and Extension Services) in Korea. Pathogenicity was confirmed by spray inoculation of healthy, 10-day-old leaves of witloof plants (two plants/isolate) with a suspension of original field isolate (106 CFU/ml). Sterile distilled water was used as negative control. The inoculated plants were incubated in a growth chamber (25°C and 95% relative humidity [RH]) overnight, then transferred to a greenhouse at 23 to 27°C and 60 to 70% RH. Characteristic leaf spot symptoms were observed on inoculated witloof plants 8 days after inoculation. No symptoms were observed on control plants. The bacterium reisolated from the inoculated leaves was confirmed by analyzing sequence of the gyrB gene with direct sequencing method of PCR products using primers gyr-F and gyr-R (2). The sequence of reisolated bacteria shared 100% similarity with inoculated ones. In LOPAT (1) tests, all isolates and the reference strain of Pseudomonas cichorii CFBP2101T (=BC2595) were levan negative, oxidase positive, potato rot negative, arginine dihydrolase negative, and tobacco hypersensitivity positive, indicative of group III (-, +, -, -, +) of fluorescent pseudomonads. The 16S rRNA (1,408 bp), and gyrB (676 bp) regions were sequenced to aid in identification of the original field isolates as well as P. cichorii CFBP 2101T (=BC2595) using reported sets of PCR primers, fD1/rP2 and gyr-F/gyr-R, respectively (2,4). Phylogenetic analyses based on partial sequences of the gyrB and the 16S rRNA of Psudomonas spp. available in GenBank, the reference strain of P. cichorii CFBP2101T (=BC2595), and the witloof field isolates were conducted using the neighbor-joining method with Juke-Cantor model of distance calculation in MEGA version 5.1 (3). The isolates and the reference strain of P. cichorii CFBP2101T (=BC2595) was clustered in one group with P. cichorii strains in both phylogenetic trees based on the two sequences. Sequences of the 16S rRNA region had a distance index value ranging from 0.000 to 0.001 between the reference strain of P. cichori CFBP2101T (GenBank JX913784) and the field isolates (JX913785 to JX913789), and ranged from 0.000 to 0.001 within the field isolates. Sequences of the gyrB region had a distance index value ranging 0.029 to 0.033 between the reference strain (JX913790) and the field isolates (JX913791 to JX913795), and ranged from 0.000 to 0.041 within the field isolates. To our knowledge, this is the first report of bacterial leaf spot of witloof caused by P. cihorii in Korea. P. cichorii has a wide host range, and an important economic impact on vegetables. The disease is expected to result in a significant economic impact on root production of witloof in Korea. References: (1) R. A. Lelliott et al. J. Appl. Bacteriol. 29:470, 1966. (2) H. Sawada et al. J. Mol. Evol. 49:627, 1999. (3) K. Tamura et al. Mol. Biol. Evol. 28:2731, 2011. (4) W. G. Weinsburg et al. J. Bacteriol. 173, 697, 1991.

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