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1.
Yeungnam Univ J Med ; 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31661759

RESUMO

Achromobacter xylosoxidans is a gram-negative bacterium that can oxidize xylose. It is commonly found in contaminated soil and water but does not normally infect immunocompetent humans. We report a case of a cavitary lung lesion associated with community-acquired A. xylosoxidans infection, which mimicked pulmonary tuberculosis or lung cancer in an immunocompetent man. The patient was hospitalized due to hemoptysis, and chest computed tomography (CT) revealed a cavitary lesion in the superior segment of the left lower lobe. We performed bronchoscopy and bronchial washing, and subsequent bacterial cultures excluded pulmonary tuberculosis and identified A. xylosoxidans. We performed antibiotic sensitivity testing and treated the patient with a 6-week course of amoxicillin/clavulanate. After 2 months, follow-up chest CT revealed complete resolution of the cavitary lesion.

2.
Int J Stem Cells ; 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31658511

RESUMO

Background and Objectives: Perivascular stem cells (PVCs) have been identified as precursors of mesenchymal stem cells (MSCs) that offer promising prospects for application in the development of cellular therapies. Although PVCs have been demonstrated to have greater therapeutic potential compared to bone marrow and adipose tissue-derived MSCs in various diseases, the regulatory role of PVCs on inflammasome activation during macrophage-mediated inflammatory responses has not been investigated. Methods and Results: In this study, we found that the PVC secretome effectively alleviates secretion of both caspase-1 and interleukin-1ß in lipopolysaccharide-primed and activated human and murine macrophages by blocking inflammasome activation and attenuating the production of mitochondrial reactive oxygen species (ROS). We further showed that the PVC secretome significantly reduces inflammatory responses and endoplasmic reticulum stress in peritoneal macrophages in a mouse model of monosodium urate-induced peritonitis. A cytokine antibody array analysis revealed that the PVC secretome contains high levels of serpin E1 and angiogenin, which may be responsible for the inhibitory effects on mitochondrial ROS generation as well as on inflammasome activation. Conclusions: Our results suggest that PVCs may be therapeutically useful for the treatment of macrophage- and inflammation-mediated diseases by paracrine action via the secretion of various biological factors.

3.
Sci Rep ; 9(1): 14007, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570746

RESUMO

Endogenous retroviruses (ERVs) have been identified at different copy numbers in various organisms. The long terminal repeat (LTR) element of an ERV has the capacity to exert regulatory influence as both a promoter and enhancer of cellular genes. Here, we describe olive flounder (OF)-ERV9, derived from chromosome 9 of the olive flounder. OF-ERV9-LTR provide binding sites for various transcription factors and showed enhancer activity. The OF-ERV9-LTR demonstrates high sequence similarity with the 3' untranslated region (UTR) of various genes that also contain seed sequences (TGTTTTG) that bind the LTR-derived microRNA(miRNA), OF-miRNA-307. Additionally, OF-miRNA-307 collaborates with transcription factors located in OF-ERV9-LTR to regulate gene expression. Taken together, our data facilitates a greater understanding of the molecular function of OF-ERV families and suggests that OF-miRNA-307 may act as a super-enhancer miRNA regulating gene activity.

4.
Korean J Ophthalmol ; 33(5): 422-429, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612652

RESUMO

PURPOSE: We investigated changes in the thickness of the peripapillary retinal nerve fiber layer (RNFL) following the onset of an epiretinal membrane (ERM) in glaucoma patients. METHODS: Among regularly monitored glaucoma patients, patients with a newly diagnosed ERM were consecutively enrolled. Before and after the onset of ERM, the RNFL thickness was measured using spectral domain optical coherence tomography, and a visual field examination was performed using a Humphrey field analyzer. Changes in RNFL thickness parameters and global indices of the visual field analyzer were assessed. RESULTS: In a total of 28 eyes from 28 patients, the average RNFL thickness increased by a mean of 4.0 ± 7.4 µm (p = 0.009) after ERM onset. There was an increase in the superior, nasal, and temporal quadrant RNFL thicknesses, and the change in the temporal RNFL thickness was significant (14.4 ± 21.2 µm, p < 0.001). However, the inferior RNFL thickness decreased by -0.6 ± 7.5 µm (p = 0.116). In the visual field examination, the mean deviation decreased significantly by -0.8 ± 1.7 dB (p = 0.038), from -14.6 to -15.4 dB. CONCLUSIONS: A significant increase in average RNFL thickness was detected following ERM onset in glaucoma patients, although there was deterioration of the mean deviation in the visual field. When ERM occurs in glaucoma patients, clinicians should be aware that RNFL thickness measurements obtained with a spectral domain optical coherence tomography may underestimate the status of glaucomatous optic neuropathy.

5.
Respir Res ; 20(1): 226, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638996

RESUMO

BACKGROUND: Muscle wasting is associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). The cross-sectional area of skeletal muscles on computed tomography (CT) could serve as a method to evaluate body composition. The present study aimed to determine the ability of CT-derived pectoralis muscle area (PMA) and pectoralis muscle density (PMD) to determine the severity of COPD and change in longitudinal pulmonary function in patients with COPD. METHODS: A total of 293 participants were enrolled in this study, a whom 222 had undergone at least two spirometry measurements within 3 years after baseline data acquisition. PMA and PMD were measured from a single axial slice of chest CT above the aortic arch at baseline. The emphysema index and bronchial wall thickness were quantitatively assessed in all scans. The generalized linear model was used to determine the correlation between PMA and PMD measurements and pulmonary function. RESULTS: PMA and PMD were significantly associated with baseline lung function and the severity of emphysema (P < 0.05). Patients with the lowest PMA and PMD exhibited significantly more severe airflow obstruction (ß = - 0.06; 95% confidence interval: - 0.09 to - 0.03]. PMA was statistically associated with COPD assessment test (CAT) score (P = 0.033). However, PMD did not exhibit statistically significant correlation with either CAT scores or modified Medical Research Council scores (P > 0.05). Furthermore, neither PMA nor PMD were associated with changes in forced expiratory volume in 1 s over a 3-year periods. CONCLUSIONS: CT-derived features of the pectoralis muscle may be helpful in predicting disease severity in patients with COPD, but are not necessarily associated with longitudinal changes in lung function.

6.
Sci Rep ; 9(1): 13901, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554879

RESUMO

Recent reports show varying results regarding peripapillary retinal nerve fibre layer (RNFL) thickness after intraocular pressure (IOP)-lowering glaucoma surgery. We hypothesised that different levels of the preoperative IOP influence RNFL thickness. A total of 60 patients (60 eyes) with glaucoma, who underwent glaucoma surgery and had a stable postoperative mean IOP < 22 mmHg, were enrolled. The RNFL thickness was measured using spectral domain optical coherence tomography, before and at 3-6 months after surgery. The preoperative peak IOP, 37.4 ± 10.8 mmHg, decreased to a postoperative mean IOP of 14.8 ± 3.5 mmHg (p < 0.001). The average RNFL thickness was significantly reduced from 75.6 ± 17.7 µm to 70.2 ± 15.8 µm (p < 0.001). In subgroup analyses, only patients with a preoperative peak IOP ≥ median value (37 mmHg) exhibited significant RNFL thinning (9.7 ± 6.6 µm, p < 0.001) associated with a higher preoperative peak IOP (r = 0.475, p = 0.008). The RNFL thinning was evident for a few months after glaucoma surgery in patients with a higher preoperative peak IOP, although the postoperative IOP was stable.

7.
Jpn J Radiol ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541398

RESUMO

PURPOSE: This study evaluated whether or not patterns of emphysema and their qualitative and quantitative severity can predict the risk of complications with post-computed tomography (CT)-guided transthoracic lung biopsy (TTLB). MATERIALS AND METHODS: Three hundred and ninety-seven patients who underwent CT-guided TTLB in 2010-2018 were retrospectively reviewed. The severity of emphysema and presence of perilesional emphysema were assessed visually using the Fleischner Society classification. Ninety seven of the 397 patients underwent quantitative analysis of emphysema. Complications, including pneumothorax, chest tube insertion, and hemorrhage, were assessed by post-TTLB CT and radiographic imaging. The grade of hemorrhage was categorized into three groups. Independent risk factors for pneumothorax and hemorrhage were assessed by univariate and multivariate logistic regression analyses. RESULTS: Pneumothorax occurred in 48.6% of cases and hemorrhage in 70.5%. Perilesional emphysema was significantly associated with pneumothorax (odds ratio 6.720; 95% confidence interval 3.265-13.831, p < 0.001) and hemorrhage (odds ratio 3.877; 95% confidence interval 1.796-8.367; p = 0.001). The severity of visual and quantitative emphysema was not a significant risk factor for pneumothorax or hemorrhage (p > 0.05). Perilesional emphysema was significantly associated with the grade of hemorrhage (p < 0.001). CONCLUSION: Perilesional emphysema can estimate the risk of iatrogenic complications from CT-guided TTLB.

8.
Arch Insect Biochem Physiol ; 102(4): e21610, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31452246

RESUMO

Aggressive red imported fire ants (RIFAs) are expanding their habitat due to active international trade and global warming. To prevent infestation and settlement, RIFAs must be removed during the quarantine process. Because RIFAs are social insects and have different morphological characteristics depending on their castes, non-ant taxonomists have difficulty confirming RIFAs based on their morphological characteristics alone. The disadvantages of previously reported RIFA molecular diagnostics are that they require additional steps, such as restriction enzyme digestion followed by agarose gel electrophoresis separation or DNA sequence verification for polymerase chain reaction (PCR)-amplified products. To overcome these drawbacks, two RIFA-specific genes were selected and used to develop diverse PCR-based RIFA molecular diagnostic techniques. We found that RIFAs could be confirmed by conventional PCR targeting of two RIFA-specific genes followed by agarose electrophoresis separation. In addition, TaqMan probe real-time PCR methods had the advantage of confirming RIFAs immediately after the reactions were completed by observing fluorescence indexes. Finally, multiplex PCRs enhanced RIFA specificity and sensitivity. The new molecular diagnostic methods developed in this study had the advantages of reducing false positive and negative results together with high specificity and sensitivity for RIFAs.

9.
Korean J Ophthalmol ; 33(4): 303-314, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31389206

RESUMO

PURPOSE: To compare the effects of cataract surgery on intraocular pressure (IOP) according to preoperative factor in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). METHODS: The medical records of 75 POAG and 95 PACG patients who underwent cataract surgery were reviewed. We classified POAG patients with a preoperative peak IOP of less than 31 mmHg and less than three medications used before surgery and PACG patients with a peak IOP of less than 42 mmHg, less than three medications used, and peripheral anterior synechiae of less than four clock hours into group 1. Patients with levels exceeding these thresholds were classified into group 2. The IOP, numbers of medications, and success rates were compared between two groups. RESULTS: At 36 months after surgery, IOP reduction in group 1 was significantly greater than that in group 2 among POAG patients (-1.7 ± 2.1 vs. -0.6 ± 2.0 mmHg, p = 0.021); however, there was no significant difference between the two groups for PACG patients (-2.5 ± 2.0 vs. -2.2 ± 3.3 mmHg, p = 0.755). The medication changes were similar between the two groups for both POAG and PACG patients. The success rate at 36 months was significantly higher in group 1 than in group 2 for POAG patients (66.7% vs. 35.7%, p = 0.009), but there was no significant difference between the two groups for PACG patients (79.1% vs. 69.2%, p = 0.264). CONCLUSIONS: For patients with relatively low peak IOP who used fewer medications before surgery, cataract surgery alone was effective for IOP control in both POAG and PACG patients. Conversely, For POAG patients with a history of higher peak IOP and who used more medications, cataract surgery was not effective in lowering IOP, whereas it resulted in relatively good IOP values in PACG patients.

10.
Drug Chem Toxicol ; : 1-8, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31305169

RESUMO

A skin irritation test using in vitro reconstructed human epidermis (RhE) models was established for hazard identification of irritant chemicals in accordance with UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) category. In this study, EpiDerm™ was used to assess skin irritation by oxybenzone and N,N-diethyl-m-toluamide (DEET), which are widely used sunscreen and insect repellent components, respectively. EpiDerm™ was applied with oxybenzone and DEET, combined and sequentially with each single dose. Epidermal morphology and differentiation/proliferation were examined microscopically. Oxybenzone and sequential administration groups were determined as nonirritant with cell viability >50% and the morphology was comparable to the human epidermis. Contrastingly, the DEET and coadministration groups exhibited cell viability <50% and poor epidermal morphology. Interleukin (IL)-1α release from substance-treated EpiDerm™ increased inversely to cell viability, suggesting the pro-inflammatory reaction was initiated by DEET. CK-10, E-cadherin, Ki-67, laminin, and ceramide were identified as relevant markers to assess oxybenzone- or DEET-induced epidermal injury. In conclusion, these results may indicate to be aware of the possible skin irritation by indiscriminate use of oxybenzone and DEET without animal testing.

11.
Korean J Ophthalmol ; 33(3): 214-221, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31179652

RESUMO

PURPOSE: To investigate the clinical features and surgical outcomes of encapsulated bleb excision with collagen matrix implantation performed in patients with failed Ahmed glaucoma valve (AGV) implantation. METHODS: Eighteen eyes of 18 patients underwent encapsulated bleb excision and collagen matrix implantation. Patients were divided into two groups by reference to intraocular pressure (IOP) after preoperative ocular massage: group 1, patients who exhibited substantial IOP reductions; and group 2, patients who did not show substantial changes in IOP. Needling was conducted in group 2. The clinical features of the two groups were compared, including IOP changes after ocular massage and needling, AGV status, and surgical outcomes 6 months after surgery. RESULTS: The mean preoperative IOP among the 18 patients was 30.6 ± 5.7 mmHg. After ocular massage, the IOPs decreased by 22 and 26 mmHg in the two patients in group 1 and the 16 patients in group 2 showed a mean IOP reduction of 1.6 ± 2.2 mmHg (p = 0.013). IOPs decreased after needling in group 2 (range, 6 to 30 mmHg; p < 0.001). Fibrovascular tissue ingrowth into the AGV was observed in the two patients in group 1 and the same ingrowth was observed in 10 of the 16 patients in group 2. Six months after surgery the mean IOP among the 18 patients decreased significantly (19.1 ± 3.2 mmHg, p < 0.001). There was no significant difference in the mean postoperative IOP at 6 months between group 1 (14.0 ± 2.8 mmHg) and group 2 (19.8 ± 2.6 mmHg, p = 0.052). CONCLUSIONS: Encapsulated bleb excision with collagen matrix implantation resulted in a significant IOP-lowering effect 6 months after surgery. Fibrovascular ingrowth into the AGV was common but did not seem to be a major cause of AGV implantation failure.


Assuntos
Colágeno/administração & dosagem , Implantes para Drenagem de Glaucoma/efeitos adversos , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Implantação de Prótese/métodos , Acuidade Visual , Adulto , Idoso , Feminino , Seguimentos , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-31172706

RESUMO

BACKGROUND: Although physical activity is known to be beneficial to lung function, few studies have been conducted to investigate the correlation between physical activity and lung function in dusty areas. Therefore, the purpose of this study is to investigate the correlation between physical activity and lung function in a Korean cohort including normal and COPD-diagnosed participants. METHODS: Data obtained from the COPD in dusty areas (CODA) cohort was analyzed for the following factors: lung function, symptoms, and information about physical activity. Information on physical activity was valuated using questionnaires, and participants were categorized into two groups: active and inactive. The evaluation of the mean lung function, modified Medical Research Council dyspnea grade scores, and COPD assessment test scores was done based on the participant physical activity using a general linear model after adjusting for age, sex, smoking status, pack-years, height, and weight. In addition, a stratification analysis was performed based on the smoking status and COPD. RESULTS: Physical activity had a correlation with high forced expiratory volume in 1 second (FEV1) among CODA cohort (p=0.03). While the active group exhibited significantly higher FEV1 compared to one exhibited by the inactive group among past smokers (p=0.02), no such correlation existed among current smokers. There was no significant difference observed in lung function after it was stratified by COPD. CONCLUSION: This study established a positive correlation between regular physical activity in dusty areas and lung function in participants.

13.
Mol Cells ; 42(4): 333-344, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31085807

RESUMO

Various genetic and environmental factors are known to be associated with chronic obstructive pulmonary disease (COPD). We identified COPD-related differentially expressed genes (DEGs) using 189 samples accompanying either adenocarcinoma (AC) or squamous cell carcinoma (SC), comprising 91 normal and 98 COPD samples. DEGs were obtained from the intersection of two DEG sets separately identified for AC and SC to exclude the influence of different cancer backgrounds co-occurring with COPD. We also measured patient samples named group 'I', which were unable to be determined as normal or COPD based on alterations in gene expression. The Gene Ontology (GO) analysis revealed significant alterations in the expression of genes categorized with the 'cell adhesion', 'inflammatory response', and 'mitochondrial functions', i.e., well-known functions related to COPD, in samples from patients with COPD. Multi-omics data were subsequently integrated to decipher the upstream regulatory changes linked to the gene expression alterations in COPD. COPD-associated expression quantitative trait loci (eQTLs) were located at the upstream regulatory regions of 96 DEGs. Additionally, 45 previously identified COPD-related miRNAs were predicted to target 66 of the DEGs. The eQTLs and miRNAs might affect the expression of 'respiratory electron transport chain' genes and 'cell proliferation' genes, respectively, while both eQTLs and miRNAs might affect the expression of 'apoptosis' genes. We think that our present study will contribute to our understanding of the molecular etiology of COPD accompanying lung cancer.


Assuntos
Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/genética , Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Comorbidade , Regulação da Expressão Gênica , Ontologia Genética , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/genética , Masculino , Mapas de Interação de Proteínas , Análise de Sequência de RNA
14.
J Neurooncol ; 143(2): 321-328, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30982199

RESUMO

PURPOSE: Lymphopenia in patients with glioblastoma (GBM) is related to treatment as well as disease progression. This retrospective study investigated the prevalence, influencing factors, recoverability, and clinical significance of lymphopenia in GBM patients treated with concomitant chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 219 patients with newly diagnosed GBM who had received at least 3 cycles of adjuvant temozolomide (TMZ) followed by CCRT with TMZ were enrolled. Serial data on complete blood cell counts, including differential cell counts, were collected just before a new phase and before every treatment cycle of the regimen. Relationships between white blood cell (WBC) variable changes and treatment modalities as well as survival were analyzed. Lymphopenia was classified using the definition of the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 92 patients (42.0%) showed decreased levels of lymphocytes (< 1500/µL) at baseline. The WBC count, absolute neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio were all significantly decreased after RT/TMZ treatment and did not recover during the adjuvant TMZ period. However, these metrics all began to recover 3 months after the last TMZ cycle, except for the lymphocyte count. The proportion of lymphopenia patients (< 1500 lymphocytes/µL) increased to 74.8% after RT/TMZ and remained steady at approximately 71.5% (range 63.7-75.3%) throughout the management period. Moreover, the number of patients with grade 3 lymphopenia (< 500 lymphocytes/µL) also increased significantly after treatment to reach 2.9% (from 0.9% at baseline). Statistically, 75.7% of lymphopenia patients were predicted to recover in a median time of 240.3 days (95% confidence interval ± 104.7 days) after TMZ withdrawal. There were no dose-dependent relationships between RT or TMZ and lymphopenia. Grade 3 (< 500 lymphocytes/µL) lymphopenia measured at 1 month after RT/TMZ predicted significantly reduced survival (13.0 months vs. 19.5 months, p = 0.011). CONCLUSION: Lymphopenia is a frequent event during GBM disease progression and treatment. Treatment-related lymphopenia is profound and prolonged and can be used as a prognostic factor for GBM patients.

15.
Clin Exp Ophthalmol ; 47(6): 757-765, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30924282

RESUMO

IMPORTANCE: Although goniotomy is known to be successful in treating congenital glaucoma, its effect in adult glaucoma patients remains unclear. BACKGROUND: To evaluate the efficacy and safety of goniotomy performed simultaneously with cataract surgery in treatment of open-angle glaucoma (OAG). DESIGN: Retrospective comparative study. PARTICIPANTS: A total of 76 patients with moderately controlled OAG (intraocular pressure [IOP] ≤ 21 mmHg using medications) undergoing cataract surgery. METHODS: Comparison of patients who underwent the conventional goniotomy during cataract surgery (combined goniotomy group) with those who underwent cataract surgery alone (phaco group). MAIN OUTCOME MEASURES: Changes in IOP and medications, and complications through 12 months. RESULTS: Baseline IOP was 18.2 ± 2.4 mmHg in the combined goniotomy group and 17.4 ± 1.9 mmHg in the phaco group; number of medications was 2.6 ± 1.1 and 2.4 ± 0.9, respectively (P > 0.05). The reduction in IOP and medication use from baseline in the combined goniotomy group was significantly greater at 12 months compared to the phaco group (-3.1 ± 2.9 mmHg vs -1.3 ± 2.4 mmHg and -1.2 ± 0.9 vs -0.7 ± 0.9, respectively, both P < 0.05). The success rate was 76.7% in the combined goniotomy group and 50.0% in the phaco group at 12 months (P = 0.021). No significant complication was observed in either group. CONCLUSIONS AND RELEVANCE: Combined goniotomy and cataract surgery showed a significantly greater reduction in IOP and number of medications compared to cataract surgery alone at 1 year after surgery, with similarly favourable safety profiles.

16.
Clin Epigenetics ; 11(1): 37, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819252

RESUMO

BACKGROUND: Ambient air pollution is associated with numerous adverse health outcomes, but the underlying mechanisms are not well understood; epigenetic effects including altered DNA methylation could play a role. To evaluate associations of long-term air pollution exposure with DNA methylation in blood, we conducted an epigenome-wide association study in a Korean chronic obstructive pulmonary disease cohort (N = 100 including 60 cases) using Illumina's Infinium HumanMethylation450K Beadchip. Annual average concentrations of particulate matter ≤ 10 µm in diameter (PM10) and nitrogen dioxide (NO2) were estimated at participants' residential addresses using exposure prediction models. We used robust linear regression to identify differentially methylated probes (DMPs) and two different approaches, DMRcate and comb-p, to identify differentially methylated regions (DMRs). RESULTS: After multiple testing correction (false discovery rate < 0.05), there were 12 DMPs and 27 DMRs associated with PM10 and 45 DMPs and 57 DMRs related to NO2. DMP cg06992688 (OTUB2) and several DMRs were associated with both exposures. Eleven DMPs in relation to NO2 confirmed previous findings in Europeans; the remainder were novel. Methylation levels of 39 DMPs were associated with expression levels of nearby genes in a separate dataset of 3075 individuals. Enriched networks were related to outcomes associated with air pollution including cardiovascular and respiratory diseases as well as inflammatory and immune responses. CONCLUSIONS: This study provides evidence that long-term ambient air pollution exposure impacts DNA methylation. The differential methylation signals can serve as potential air pollution biomarkers. These results may help better understand the influences of ambient air pollution on human health.


Assuntos
Poluição do Ar/análise , Metilação de DNA , Doença Pulmonar Obstrutiva Crônica/genética , Sequenciamento Completo do Genoma/métodos , Idoso , Idoso de 80 Anos ou mais , Poluição do Ar/efeitos adversos , Estudos de Coortes , Metilação de DNA/efeitos dos fármacos , Epigênese Genética , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Material Particulado/análise , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , República da Coreia
17.
Environ Res ; 172: 358-366, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30825686

RESUMO

The Korean CHildren's ENvironmental health Study (Ko-CHENS) is a nationwide prospective birth cohort showing the correlation between the environmental exposures and the health effects to prevent the environmental diseases in children, and it provides the guidelines for the environmental hazardous factors, applying the life-course approach to the environmental-health management system. The Ko-CHENS consists of 5000 Core and 65,000 Main Cohorts. The children in the Core Cohort are followed up at 6 months, every year before their admission into the elementary school, and every 3 years from the first year after this admission. The children in the Cohort will be followed up through the data links (Statistics Korea, National Health Insurance Service [NHIS], and Ministry of Education). The individual biospecimens will be analyzed for 19 substances. The long-term-storage biological samples will be used for the further substance analysis. The Ko-CHENS will investigate whether the environmental variables including the perinatal outdoor and indoor factors and the greenness contribute causally to the health outcomes in the children and adolescents. In addition to the individual surveys, the assessments of the outdoor exposures and health outcomes will use the national air-quality monitoring data and claim data of the NHIS, respectively. The two big-data forms of the Ko-CHENS are as follows: The Ko-CHENS data that can be linked with the nationally registered NHIS health-related database, including the medical utilization and the periodic health screening, and the birth/mortality database in the Statistics; the other is the Big-CHENS dataset that is based on the NHIS mother delivery code, for which the follow-up of almost 97% of the total birth population is expected. The Ko-CHENS is a very cost-effective study that fully exploits the existing national big-data systems with the data linkage.

19.
BMC Infect Dis ; 19(1): 151, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760247

RESUMO

BACKGROUND: Vitamin D levels are associated with the extent of mycobactericidal activity. Interleukin (IL)-15 and IL-32 play roles in the vitamin D-mediated tuberculosis (TB) defense mechanism. Vitamin D induces IL-1ß, which plays an important role in terms of resistance to TB. We evaluated whether the levels of vitamin D-related cytokines distinguished between those with active TB and latent TB infection (LTBI). METHODS: In total, 50 TB-infected patients (25 with active TB and 25 with LTBI following a TB outbreak in a high school) were enrolled. Plasma 25-hydroxyvitamin D (25[OH]D), IL-15, IL-32, and IL-1ß levels were measured via enzyme-linked immunosorbent assays. Mycobacterium tuberculosis-specific antigen-induced and unstimulated cytokine levels were measured in the supernatants of the QuantiFERON TB Gold-In-Tube (QFT-GIT) assay. RESULTS: Plasma 25(OH)D and plasma IL-15 levels were lower in patients with active TB than in LTBI subjects (25(OH)D: 16.64 ng/mL vs. 21.6 ng/mL, P = 0.031; IL-15: 148.9 pg/mL vs. 189.8 pg/mL, P = 0.013). Plasma 25(OH)D levels correlated with the plasma levels of IL-15 and IL-1ß in TB-infected patients. In addition, the plasma 25(OH)D levels correlated positively with the level of unstimulated IL-15 (IL-15nil) and negatively with that of TB antigen-stimulated IL-32 (IL-32TB) in QFT-GIT supernatants. Although the IL-15nil and IL-15TB levels were higher in LTBI subjects than patients with active TB, the IL-32nil and IL-32TB levels were higher in the latter patients. A combination of the IL-15nil and IL-32TB levels accurately predicted 91.3% of active TB patients and latent subjects, with an area under the curve of 0.964. CONCLUSIONS: Our preliminary data showed that the levels of the vitamin D-related cytokines IL-15 and IL-32 differed between active TB patients and LTBI subjects. This result might be used as a basic data for developing biomarkers distinguishing between active TB and LTBI.


Assuntos
Citocinas/sangue , Tuberculose Latente/sangue , Tuberculose/sangue , Vitamina D/sangue , Adolescente , Biomarcadores/sangue , Testes Diagnósticos de Rotina , Surtos de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-15/sangue , Interleucinas/sangue , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Masculino , Mycobacterium tuberculosis/imunologia , República da Coreia/epidemiologia , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Vitamina D/análogos & derivados
20.
Nat Genet ; 51(3): 494-505, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804561

RESUMO

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.


Assuntos
Predisposição Genética para Doença/genética , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Idoso , Asma/genética , Estudos de Casos e Controles , Feminino , Expressão Gênica/genética , Loci Gênicos/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Fibrose Pulmonar/genética , Fumar/genética
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