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1.
Int J Aging Hum Dev ; : 914150241240114, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528732

RESUMO

Applying latent growth mixture modeling (GMM), this study delves into the examination of self-esteem trajectories in a sample of 5,597 older adults over a nine-year period. Four distinct patterns of self-esteem changes have emerged: low, decreasing, increasing, and high. Additionally, the study explores the relationships between each trajectory and various predictors encompassing demographic factors, socioeconomic status, health, and interpersonal relationships. The findings highlight the significance of these factors in predicting the likelihood of an individual following a specific self-esteem trajectory. Notably, maintaining employment, fostering satisfactory social relationships, and being free of frequent depressive feelings emerged as strong predictors for the stability and increase of high self-esteem. Intriguingly, an average or above-average income was unexpectedly associated with lower levels of self-esteem. The study emphasizes the contribution of GMM to advancing aging research.

2.
Int J Mol Sci ; 24(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38069324

RESUMO

Tissue-specific gene expression generates fundamental differences in the function of each tissue and affects the characteristics of the tumors that are created as a result. However, it is unclear how much the tissue specificity is conserved during grafting of the primary tumor into an immune-compromised mouse model. Here, we performed a comparative RNA-seq analysis of four different primary-patient derived xenograft (PDX) tumors. The analysis revealed a conserved RNA biotype distribution of primary-PDX pairs, as revealed by previous works. Interestingly, we detected significant changes in the splicing pattern of PDX, which was mainly comprised of skipped exons. This was confirmed by splicing variant-specific RT-PCR analysis. On the other hand, the correlation analysis for the tissue-specific genes indicated overall strong positive correlations between the primary and PDX tumor pairs, with the exception of gastric cancer cases, which showed an inverse correlation. These data propose a tissue-specific change in splicing events during PDX formation as a variable factor that affects primary-PDX integrity.


Assuntos
Processamento Alternativo , Neoplasias Gástricas , Animais , Camundongos , Humanos , Neoplasias Gástricas/patologia , Splicing de RNA/genética , Análise de Sequência de RNA
3.
J Obstet Gynaecol ; 40(8): 1090-1095, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31826681

RESUMO

Clinical performance of the Momguard non-invasive prenatal test (NIPT) was evaluated in a cohort of Korean pregnant women. The foetal trisomies 21, 18 and 13 (T21, T18 and T13) were screened by low-coverage massive parallel sequencing in the maternal blood. Among the 1011 confirmed samples, 32 cases (3.2%) had positive NIPT results. Of these positive cases, 20 cases of T21, all cases of T18 and two cases of T13 had concordant karyotype findings. Only one case out of the remaining 979 negative NIPT samples showed a false negative result. The overall sensitivity and specificity of Momguard to detect the three chromosomal aneuploidies were 96.8% and 99.8%, respectively. Momguard is a clinically useful tool for the detection of T21, T18 and T13 in singleton pregnancy. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.Impact StatementWhat is already known on this subject? The NIPT approach using massive parallel sequencing (MPS) showed high sensitivity and specificity in various clinical studies. These results are based on analysis systems using their own bioinformatics algorithms.What the results of this study add? When this NIPT technology was introduced in Korea, the first biological specimens collected in Korea were transported overseas for processing in overseas laboratories and analysed by other country's analysis methods. We needed our own NIPT algorithm and developed Momguard NIPT for the first time in Korea. This study attempted to evaluate this Momguard NIPT protocol prospectively in a large number of samples obtained from three Korean hospitals.What the implications are of these findings for clinical practice and/or further research? The overall sensitivity and specificity to identify T13, T18 and T21 were 96.8% and 99.8%, respectively. These accuracy values were comparable to that of other studies. From this study, we found that Momguard is a clinically useful tool for the detection of three chromosomal aneuploidies. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.


Assuntos
Síndrome de Down/diagnóstico , Teste Pré-Natal não Invasivo/estatística & dados numéricos , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Adulto , Síndrome de Down/embriologia , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , República da Coreia , Sensibilidade e Especificidade , Síndrome da Trissomia do Cromossomo 13/embriologia , Síndrome da Trissomía do Cromossomo 18/embriologia
4.
Breast Cancer Res Treat ; 161(1): 95-102, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27783279

RESUMO

PURPOSE: This study was performed to evaluate the frequency of mutations in CHEK2, PALB2, MRE11, and RAD50 among Korean patients at high risk for hereditary breast cancer. METHODS: A total of 235 Korean patients with hereditary breast cancer who tested negative for BRCA1/2 mutation were enrolled to this study. Entire coding regions of CHEK2, PALB2, MRE11, and RAD50 were analyzed using massively parallel sequencing (MPS). Sequence variants detected by MPS were confirmed by Sanger sequencing. RESULTS: Six patients (2.5 %) were found to have pathogenic variants in CHEK2 (n = 1), PALB2 (n = 2), MRE11 (n = 1), and RAD50 (n = 2). Among the pathogenic variants, PALB2 c.2257C>T was previously reported in other studies, while CHEK2 c.1245dupC, PALB2 c.1048C>T, MRE11 c.1773_1774delAA, RAD50 c.1276C>T, and RAD50 c.3811_3813delGAA were newly identified in this study. A total of 15 missense variants were found in the four genes among 26 patients; 7 patients had a variant in CHEK2, 11 in PALB2, 2 in MRE11, and 6 in RAD50. When in silico analyses were performed to the 15 missense variants, six variants (CHEK2 c.686A>G, PALB2 c.1492G>T, PALB2 c.3054G>C, MRE11 c.140C>T, RAD50 c.1456C>T, and RAD50 c.3790C>T) were predicted to be deleterious. CONCLUSIONS: Pathogenic variants in CHEK2, PALB2, MRE11, and RAD50 were detected in a small proportion of Korean patients with features of hereditary breast cancer.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Quinase do Ponto de Checagem 2/genética , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Mutação em Linhagem Germinativa , Proteína Homóloga a MRE11/genética , Taxa de Mutação , Hidrolases Anidrido Ácido , Alelos , Substituição de Aminoácidos , Biomarcadores Tumorais , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Risco
5.
Anal Chem ; 88(5): 2871-6, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26828904

RESUMO

We developed a whole-cell surface plasmon resonance (SPR) sensor based on a leucine auxotroph of Escherichia coli displaying a gold-binding protein (GBP) in response to cell growth and applied this sensor to the diagnosis of maple syrup urine disease, which is represented by the elevated leucine level in blood. The leucine auxotroph was genetically engineered to grow displaying GBP in a proportion to the concentration of target amino acid leucine. The GBP expressed on the surface of the auxotrophs directly bound to the golden surface of an SPR chip without the need for any additional treatment or reagents, which consequently produced SPR signals used to determine leucine levels in a test sample. Gold nanoparticles (GNPs) were further applied to the SPR system, which significantly enhanced the signal intensity up to 10-fold by specifically binding to GBP expressed on the cell surface. Finally, the diagnostic utility of our system was demonstrated by its employment in reliably determining different statuses of maple syrup urine disease based on a known cutoff level of leucine. This new approach based on an amino acid-auxotrophic E. coli strain expressing a GBP that binds to an SPR sensor holds great promise for detection of other metabolic diseases of newborn babies including homocystinuria and phenylketonuria, which are also associated with abnormal levels of amino acids.


Assuntos
Escherichia coli/química , Ouro/química , Leucina/análise , Doença da Urina de Xarope de Bordo/diagnóstico , Ressonância de Plasmônio de Superfície/instrumentação
6.
J Sex Med ; 12(4): 966-74, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25648342

RESUMO

INTRODUCTION: Both testosterone therapy and chronic treatment with phosphodiesterase type 5 inhibitors (PDE5Is) have positive effects on the histology of penile corpora and erectile function. However, few clinical studies have evaluated the efficacy of combination therapy with both testosterone replacement and chronic PDE5Is. AIM: This study was designed to evaluate the efficacy and safety of combination treatment with long-acting injectable testosterone undecanoate (TU) and a once-daily tadalafil 5 mg for erectile dysfunction with testosterone deficiency syndrome. METHODS: Sixty patients were consecutively enrolled and followed for 36 weeks. Thirty patients were randomly assigned to group I and received 1,000 mg of parenteral TU on day 1, followed by additional injections at weeks 6 and 18 with on-demand tadalafil 10-20 mg during the 30 weeks of treatment. The remaining 30 patients received the same dose and schedule of TU as group I, and were prescribed once-daily tadalafil 5 mg during 30 weeks. MAIN OUTCOME MEASURES: Serological tests were performed, and the International Index of Erectile Function (IIEF), Aging Males' Symptoms (AMS) questionnaires, and Global Assessment Question (GAQ) were administered to the patients. RESULTS: Total IIEF and AMS scores were significantly improved during the 30 weeks of treatment in both groups. When IIEF scores were compared between the two groups, group II showed better symptom scores than group I at weeks 6 and 30. A similar pattern was observed when comparing AMS scores between the groups. At week 36, changes in IIEF and AMS scores that indicated worsened symptoms compared with week 30 were observed in both groups; group II showed better symptom scores than group I. On the GAQ, the ratio of patients reporting improvement in erectile function was significantly higher in group II than group I. CONCLUSIONS: The combination of long-acting injectable TU and once-daily tadalafil 5 mg produced a significant improvement in erectile function. Moreover, the improvement in erectile function was well maintained, even after the cessation of treatment.


Assuntos
Carbolinas/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Testosterona/análogos & derivados , Testosterona/deficiência , Adulto , Idoso , Preparações de Ação Retardada , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/efeitos dos fármacos , Síndrome , Tadalafila , Testosterona/administração & dosagem , Testosterona/uso terapêutico
7.
J Nanosci Nanotechnol ; 15(10): 7955-61, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26726446

RESUMO

In this study, a microscale well-plate colorimetric assay for the multiplexed detection of glucose and cholesterol in clinical human blood samples has been developed. This system utilized one-pot nanocomposite entrapping Fe3O4 magnetic nanoparticles (MNPs) as peroxidase mimetics and glucose oxidase (GOx)/cholesterol oxidase (ChOx) in mesoporous silica to detect glucose and cholesterol in blood samples. The sensing mechanism involves the generation of H2O2 by the catalytic action of an immobilized oxidase on the target molecules in the sample. This subsequently activates the MNPs in the mesopores, thereby leading to the conversion of the substrate into a colored end product. This strategy is used to detect the target glucose or cholesterol molecules in the concentration range of 15-250 mg/dL. The response is highly linear and the lower detection limit is 7.5 mg/dL. The aforementioned colorimetric assay is extremely convenient, and it exhibits a high degree of linearity, precision, and reproducibility when employing real human blood samples. Therefore, this assay can be used in clinical practice for the multiplexed and reliable quantification of glucose and cholesterol.


Assuntos
Técnicas Biossensoriais/métodos , Glicemia/metabolismo , Colesterol Oxidase/química , Colesterol/sangue , Glucose Oxidase/química , Colorimetria/métodos , Enzimas Imobilizadas/química , Humanos , Peróxido de Hidrogênio/química , Sensibilidade e Especificidade
8.
Anal Chem ; 86(5): 2489-96, 2014 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-24475885

RESUMO

A cell-based assay system for simultaneous quantification of the three amino acids, phenylalanine (Phe), methionine (Met), and leucine (Leu) in a single biological sample, was developed and applied in the multiplex diagnosis of three key metabolic diseases of newborn babies. The assay utilizes three Escherichia coli auxotrophs, which grow only in the presence of the corresponding target amino acids and which contain three different fluorescent reporter plasmids that produce distinguishable fluorescence signals (red, green, and cyan) in concert with cell growth. To mixtures of the three auxotrophs, immobilized on agarose gels arrayed on a well plate, is added a test sample. Following incubation, the concentrations of the three amino acids in the sample are simultaneously determined by measuring the intensities of three fluorescence signals that correspond to the reporter plasmids. The clinical utility of this assay system was demonstrated by employing it to identify metabolic diseases of newborn babies through the quantification of Phe, Met, and Leu in clinically derived dried blood spot specimens. The general strategy developed in this effort should be applicable to the design of new assay systems for the quantification of multiple amino acids derived from complex biological samples and, as such, to expand the utilization of cell-based analytical systems that replace conventional, yet laborious methods currently in use.


Assuntos
Aminoácidos/metabolismo , Escherichia coli/metabolismo , Corantes Fluorescentes/metabolismo , Sequência de Bases , Primers do DNA , Humanos , Recém-Nascido , Limite de Detecção , Reação em Cadeia da Polimerase
9.
Anal Chem ; 85(22): 11083-9, 2013 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-24143930

RESUMO

A new cell-based galactose assay system, which is comprised of two bioluminescent Escherichia coli strains immobilized within an agarose gel arrayed on a well plate, has been developed. For this purpose, a galT knockout strain [galT(-) cell] of E. coli was genetically constructed so that cell growth is not promoted by galactose but rather by glucose present in a sample. Another E. coli W strain (normal cell), which grows normally in the presence of either glucose or galactose, was employed. A luminescent reporter gene, which produces luminescence as cells grow, was inserted into both of the E. coli strains, so that cell growth could be monitored in a facile manner. The two strains were separately grown for 4 h on gel arrays to which test samples were individually supplied. The relative luminescence unit (RLU) values caused by cell growth were determined for each array, one of which is resulted by glucose only and the other of which is resulted by both glucose and galactose present in the sample. By employing this protocol, galactose concentrations present in the test sample are reflected in the differences between the RLU values for each array. The practical utility of the new assay system was demonstrated by its use in determining galactose levels in clinical blood spot specimens coming from newborn babies. Because it can be employed to diagnosis of galactosemia in newborn babies in a more rapid, convenient, and cost-effective manner, this cell-based solid-phase galactose assay system should become a powerful alternative to conventional methods, which require labor-intensive and time-consuming procedures and/or complicated and expensive equipment.


Assuntos
Biomarcadores/análise , Escherichia coli/química , Galactose/análise , Galactosemias/diagnóstico , Glucose/análise , Medições Luminescentes/métodos , Escherichia coli/citologia , Galactosemias/sangue , Humanos , Lactente
10.
Behav Brain Funct ; 9: 1, 2013 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-23295062

RESUMO

BACKGROUND: The purpose of this study was to investigate the association between the ionotropic and glutamate receptors, N-methyl D-asparate 2A (GRIN2A) and 2B (GRIN2B), and the metabotropic glutamate receptor mGluR7 (GRM7) gene polymorphisms and attention-deficit hyperactivity disorder (ADHD) in Korean population. METHODS: We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 149 trios, and compared scores from the continuous performance test (CPT), the Children's Depression Inventory (CDI), and the State-Trait Anxiety Inventory for Children (STAIC) according to the genotype of the glutamate receptor genes. RESULTS: There were no significant differences in the genotype or allele frequencies of the GRIN2A rs8049651, GRIN2B rs2284411, or GRM7 rs37952452 polymorphisms between the ADHD and control groups. For 148 ADHD trios, the TDT analysis also showed no preferential transmission of the GRIN2A rs8049651 or GRIN2B rs2284411 polymorphisms. However, the TDT analysis of the GRM7 rs3792452 polymorphism showed biased transmission of the G allele (χ2 = 4.67, p = 0.031). In the ADHD probands, the subjects with GG genotype in the GRM7 rs37952452 polymorphism had higher mean T-scores for omission errors on the CPT than did those with the GA or AA genotype (t = 3.38, p = 0.001). In addition, the ADHD subjects who were homozygous for the G allele in the GRM7 rs37952452 polymorphism had higher STAIC-T (t = 5.52, p < 0.001) and STAIC-S (t = 2.74, p = 0.007) scores than did those with the GA or AA genotype. CONCLUSIONS: These results provide preliminary evidence of an association between the GRM7 rs37952452 polymorphism and selective attention deficit and anxiety found within the Korean ADHD population.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Receptores de Glutamato Metabotrópico/genética , Sintomas Afetivos/complicações , Sintomas Afetivos/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estudos de Casos e Controles , Criança , Interpretação Estatística de Dados , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Estudos de Associação Genética , Genótipo , Ácido Glutâmico/genética , Humanos , Desequilíbrio de Ligação , Masculino , Testes Neuropsicológicos , Polimorfismo Genético/genética , Escalas de Graduação Psiquiátrica , Desempenho Psicomotor/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia/epidemiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Escalas de Wechsler
11.
Front Psychol ; 14: 1192859, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022963

RESUMO

Focusing on employees, this study examined the respective mediating and moderating effects of affective organizational commitment and organizational learning capacity in the relationship between core self-evaluation and innovation work behavior. We collected data via an online survey from 330 office workers at midsize and large companies in a metropolitan area of South Korea. The results of analyzing the data using PROCESS macro were as follows: (1) core self-evaluation was positively related to innovative work behavior; (2) the relationship was mediated by affective organizational commitment; (3) the relationship was buffered by organizational learning capacity, such that a higher level of organizational learning capacity diminished the impact of core self-evaluation on innovative wok behavior; and (4) the conditional effect of core self-evaluation on innovative work behavior existed only in the group of a low level of organizational learning capacity. Based on these findings, we suggested implications for theory building, research, and practice.

12.
Materials (Basel) ; 16(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37763537

RESUMO

This study investigated defect formation and strain distribution in high-Mg-content Al-Mg alloys during normal rolling and cross-rolling processes. The finite element analysis (FEA) revealed the presence of wave defects and strain localization-induced zipper cracks in normal cold rolling, which were confirmed by the experimental results. The concentration of shear strain played a significant role in crack formation and propagation. However, the influence of wave defects was minimal in the cross-rolling process, which exhibited a relatively uniform strain distribution. Nonetheless, strain concentration at the edge and center regions led to the formation of zipper cracks and edge cracks, with more pronounced propagation observed in the experiments compared to FEA predictions. Furthermore, texture evolution was found to be a crucial factor affecting crack propagation, particularly with the development of the Goss texture component, which was observed via electron backscattered diffraction analysis at bending points. The Goss texture hindered crack propagation, while the Brass texture allowed cracks to pass through. This phenomenon was consistent with both FEA and experimental observations. To mitigate edge crack formation and propagation, potential strategies involve promoting the formation of the Goss texture at the edge through alloy and process conditions, as well as implementing intermediate annealing to alleviate stress accumulation. These measures can enhance the overall quality and reliability of Al-Mg alloys during cross-rolling processes. In summary, understanding the mechanisms of defect formation and strain distribution in Al-Mg alloys during rolling processes is crucial for optimizing their mechanical properties. The findings of this study provide insights into the challenges associated with wave defects, strain localization, and crack propagation. Future research and optimization efforts should focus on implementing strategies to minimize defects and improve the overall quality of Al-Mg alloys in industrial applications.

13.
Nat Genet ; 55(2): 221-231, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36624345

RESUMO

Despite advances in predicting physical peptide-major histocompatibility complex I (pMHC I) binding, it remains challenging to identify functionally immunogenic neoepitopes, especially for MHC II. By using the results of >36,000 immunogenicity assay, we developed a method to identify pMHC whose structural alignment facilitates T cell reaction. Our method predicted neoepitopes for MHC II and MHC I that were responsive to checkpoint blockade when applied to >1,200 samples of various tumor types. To investigate selection by spontaneous immunity at the single epitope level, we analyzed the frequency spectrum of >25 million mutations in >9,000 treatment-naive tumors with >100 immune phenotypes. MHC II immunogenicity specifically lowered variant frequencies in tumors under high immune pressure, particularly with high TCR clonality and MHC II expression. A similar trend was shown for MHC I neoepitopes, but only in particular tissue types. In summary, we report immune selection imposed by MHC II-restricted natural or therapeutic T cell reactivity.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Epitopos/genética , Linfócitos T , Peptídeos/química , Peptídeos/metabolismo
14.
Sci Rep ; 13(1): 22482, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110532

RESUMO

Genomic hypomethylation has recently been identified as a determinant of therapeutic responses to immune checkpoint blockade (ICB). However, it remains unclear whether this approach can be applied to cell-free DNA (cfDNA) and whether it can address the issue of low tumor purity encountered in tissue-based methylation profiling. In this study, we developed an assay named iMethyl, designed to estimate the genomic hypomethylation status from cfDNA. This was achieved through deep targeted sequencing of young LINE-1 elements with > 400,000 reads per sample. iMethyl was applied to a total of 653 ICB samples encompassing lung cancer (cfDNA n = 167; tissue n = 137; cfDNA early during treatment n = 40), breast cancer (cfDNA n = 91; tissue n = 50; PBMC n = 50; cfDNA at progression n = 44), and ovarian cancer (tissue n = 74). iMethyl-liquid predicted ICB responses accurately regardless of the tumor purity of tissue samples. iMethyl-liquid was also able to monitor therapeutic responses early during treatment (3 or 6 weeks after initiation of ICB) and detect progressive hypomethylation accompanying tumor progression. iMethyl-tissue had better predictive power than tumor mutation burden and PD-L1 expression. In conclusion, our iMethyl-liquid method allows for reliable noninvasive prediction, early evaluation, and monitoring of clinical responses to ICB therapy.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , Neoplasias Pulmonares , Humanos , Feminino , Ácidos Nucleicos Livres/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Leucócitos Mononucleares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Genômica/métodos , Pulmão/patologia , Biomarcadores Tumorais/genética
15.
Breast Cancer Res Treat ; 134(3): 1315-26, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22798144

RESUMO

This investigation is aimed at evaluating the epidemiologic characteristics of BRCA1/2 germline mutations in Korean patients with breast and ovarian cancer (BOC). We analyzed the entire mutational data of BRCA1/2 genes in BOC patients who were tested in Korea since the first Korean report of BRCA1 mutation in 1995 with the exception of the data covered in the Korean Hereditary Breast Cancer (KOHBRA) study, the project launched in 2007 for establishing BRCA1/2 carrier cohorts in Korea. In total, BRCA1/2 gene mutations of 3,922 Korean BOC patients were evaluated, including the unpublished data of 2,139 breast cancer patients examined by four Korean institutions and the data of 1,783 BOC patients covered in ten previous reports. Overall, 420 (150 distinct) pathogenic mutations were identified, 211 (73 distinct) in BRCA1 and 209 (77 distinct) in BRCA2. The majority (134 of 150) of the distinct mutations resulted in premature termination codon of the BRCA1/2 translation. BRCA1 c.4186-1593_4676-1465del was the only large genomic rearrangements mutation. Out of 150 distinct BRCA1/2 mutations, 84 (56 %) mutations were considered specific to Korean BOC. Eighty-five BRCA1/2 mutations were detected in at least two unrelated patients. These recurrent mutations account for 84.5 % (355 of 420) of mutations detected in the Korean population. In the pooled mutational data of BRCA1/2 genes, this study discovered the prevalence of BRCA1/2 mutations in the Korean BOC patients is similar to those found in other ethnic groups. Large genomic rearrangements in BRCA1/2 genes were infrequently detected among the Korean patients with BOC. There were several BRCA1/2 mutation candidates for founder mutations. To further establish a Korean cohort for BRCA1/2 mutations, the nationwide KOHBRA study is in progress.


Assuntos
Povo Asiático/genética , Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Mutação , Neoplasias Ovarianas/genética , Neoplasias da Mama/epidemiologia , Feminino , Mutação em Linhagem Germinativa , Humanos , Neoplasias Ovarianas/epidemiologia , Prevalência , República da Coreia/epidemiologia
16.
Analyst ; 137(5): 1137-43, 2012 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-22258062

RESUMO

A colorimetric method for quantification of galactose, which utilizes a nanostructured multi-catalyst system consisting of Fe(3)O(4) magnetic nanoparticles (MNPs) and galactose oxidase (Gal Ox) simultaneously entrapped in large pore sized mesocellular silica, is described. Gal Ox, immobilized in a silica matrix, promotes reaction of galactose to generate H(2)O(2) that subsequently activates MNPs in silica mesopores to convert a colorimetric substrate into a colored product. By using this colorimetric method, galactose can be specifically detected. Along with excellent reusability via application of simple magnetic capturing, enhanced operational stability was achieved by employing a cross-linked enzyme aggregate (CLEA) method for Gal Ox immobilization. This protocol leads to effective prevention of enzyme leaching from the pores of mesocellular silica. The analytical utility of the new colorimetric biosensor was demonstrated by its use in diagnosing galactosemia, a genetic metabolic disorder characterized by the inability to utilize galactose, through analysis of clinical dried blood spot specimens. A microscale well-plate format was employed that possesses a multiplexing capability. The multi-catalyst system entrapping Gal Ox and MNPs represents a new approach for rapid, convenient, and cost-effective quantification of galactose in human blood and it holds promise as an alternative method for galactosemia diagnosis, replacing the laborious procedures that are currently in use.


Assuntos
Materiais Biomiméticos/química , Colorimetria/métodos , Galactose Oxidase/química , Galactose/análise , Imãs/química , Nanopartículas/química , Peroxidase/metabolismo , Catálise , Teste em Amostras de Sangue Seco , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Galactose/sangue , Galactose Oxidase/metabolismo , Galactosemias/sangue , Galactosemias/diagnóstico , Humanos , Modelos Lineares , Porosidade , Dióxido de Silício/química
17.
J Anim Sci Technol ; 64(3): 599-602, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35709122

RESUMO

A new bacteriocin-producing lactic acid bacteria isolated from kimchi was identified as Lactococcus lactis JNU 534, presenting preservative properties for foods of animal origin. In this study, we present the complete genome sequence of the bacterial strain JNU 534. The final complete genome assembly consists of one circular chromosome (2,443,687 bp [base pair]) with an overall GC (guanine-cytosine) content of 35.2%, one circular plasmid sequence (46,387 bp) with a GC content of 34.5%, and one circular contig sequence (7,666 bp) with a GC content of 36.2%.

18.
Anal Chem ; 83(8): 3089-95, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21413693

RESUMO

A cell-based quantitative assay system for Hcy has been developed by utilizing two Escherichia coli auxotrophs that grow in the presence of methionine (Met) and either homocysteine (Hcy) or Met, respectively. A bioluminescent reporter gene, which produces luminescence as cells grow, was inserted into the auxotrophs, so that cell growth can be readily determined. When the relative luminescence unit (RLU) values from the two auxotrophs immobilized within agarose gels arrayed on a well plate were measured, the amount of Hcy was quantitatively determined on the basis of differences between two RLU values corresponding to cell growth of two auxotrophs with excellent levels of precision and reproducibility. Finally, the diagnostic utility of this assay system was verified by its employment in reliably determining different stages of hyperhomocysteinemia in human plasma samples providing CVs of within and between assays that are less than 2.9% and 7.1%, respectively, and recovery rates of within and between assays that are in the range of 99.1-103.5% and 97.5-105.5%, respectively. In contrast to existing conventional methods, the new system developed in this effort is simple, rapid, and cost-effective. As a result, it has great potential to serve as a viable alternative for Hcy quantification in the diagnosis of hyperhomocysteinemia.


Assuntos
Escherichia coli/química , Hiper-Homocisteinemia/sangue , Luminescência , Medições Luminescentes/métodos , Escherichia coli/citologia , Escherichia coli/crescimento & desenvolvimento , Humanos , Sensibilidade e Especificidade
19.
Analyst ; 136(8): 1573-9, 2011 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-21321686

RESUMO

The operation of an electrochemical real-time PCR system, based on intercalative binding of methylene blue (MB) with dsDNA, has been demonstrated. PCR was performed on a fabricated electrode-patterned glass chip containing MB while recording the cathodic current peak by measuring the square wave voltammogram (SWV). The current peak signal was found to decrease with an increase in the PCR cycle number. This phenomenon was found to be mainly a consequence of the lower apparent diffusion rate of the MB-DNA complex (D(b) = 6.82 × 10(-6) cm(2) s(-1) with 612 bp dsDNA) as compared to that of free MB (D(f) = 5.06 × 10(-5) cm(2) s(-1)). Utilizing this signal changing mechanism, we successfully demonstrated the feasibility of an electrochemical real-time PCR system by accurately quantifying initial copy numbers of Chlamydia trachomatis DNA templates on a direct electrode chip. A standard calibration plot of the threshold cycle (C(t)) value versus the log of the input template quantity demonstrated reliable linearity and a good PCR efficiency (106%) that is comparable to that of a conventional TaqMan probe-based real time PCR. Finally, the system developed in this effort can be employed as a key technology for the achievement of point-of-care genetic diagnosis based on the electrochemical real-time PCR.


Assuntos
DNA/química , Técnicas Eletroquímicas/métodos , Azul de Metileno/química , Reação em Cadeia da Polimerase/métodos , Chlamydia trachomatis/genética , Difusão , Eletrodos , Dosagem de Genes , Sistemas Automatizados de Assistência Junto ao Leito
20.
J Korean Med Sci ; 26(1): 85-91, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21218035

RESUMO

We developed and validated a novel Korean prostate cancer risk calculator (KPCRC) for predicting the probability of a positive initial prostate biopsy in a Korean population. Data were collected from 602 Koreans who underwent initial prostate biopsies due to an increased level of prostate-specific antigen (PSA), a palpable nodule upon digital rectal examination (DRE), or a hypoechoic lesion upon transrectal ultrasound (TRUS). The clinical and laboratory variables were analyzed by simple and multiple logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was computed to compare its performance to PSA testing alone. Prostate cancer was detected in 172 (28.6%) men. Independent predictors included age, DRE findings, PSA level, and prostate transitional zone volume. We developed the KPCRC using these variables. The AUC for the selected model was 0.91, and that of PSA testing alone was 0.83 (P < 0.001). The AUC for the selected model with an additional dataset was 0.79, and that of PSA testing alone was 0.73 (P = 0.004). The calculator is available on the website: http://pcrc.korea.ac.kr. The KPCRC improved the performance of PSA testing alone in predicting the risk of prostate cancer in a Korean population. This calculator would be a practical tool for physicians and patients.


Assuntos
Exame Retal Digital , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Área Sob a Curva , Biópsia por Agulha , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Curva ROC , República da Coreia , Risco , Ultrassonografia
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