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EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury

  • Hong, Ji Young;Shin, Mi Hwa;Chung, Kyung Soo;Kim, Eun Young;Jung, Ji Ye;Kang, Young Ae;Kim, Young Sam;Kim, Se Kyu;Chang, Joon;Park, Moo Suk
    • Tuberculosis and Respiratory Diseases
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    • v.78 no.3
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    • pp.218-226
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    • 2015
  • Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury. Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure). Results: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group ($4.30{\pm}2.93$ vs. $11.45{\pm}1.20$, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: $11.33{\times}10^4{\pm}8.84{\times}10^4$ vs. IgG+LPS: $208.0{\times}10^4{\pm}122.6{\times}10^4$; p=0.018) and total protein concentrations (EphA2 mAb+LPS: $0.52{\pm}0.41mg/mL$ vs. IgG+LPS: $1.38{\pm}1.08mg/mL$; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase $110{\gamma}$, phospho-Akt, nuclear factor ${\kappa}B$, and proinflammatory cytokines. Conclusion: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

Relationship between Exhaled Nitric Oxide and Levels of Asthma Control in Asthma Patients Treated with Inhaled Corticosteroid

  • Han, Chang-Hee;Park, You-Il;Kwak, Hyun-Jung;Kim, Sa-Il;Kim, Tae-Hyung;Sohn, Jang-Won;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo;Kim, Sang-Heon
    • Tuberculosis and Respiratory Diseases
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    • v.71 no.2
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    • pp.106-113
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    • 2011
  • Background: While asthma control is defined as the extent to which the various manifestations of asthma are reduced by treatment, current guidelines of asthma recommend assessment of asthma control without consideration of airway inflammation. Our aim was to investigate the relationships between fractional exhaled nitric oxide (FeNO), a reliable marker of airway inflammation, and levels of asthma control in patients treated with inhaled corticosteroids (ICS). Methods: We enrolled 71 adult patients with asthma who had been treated with ICS for more than four months. FeNO was measured and spirometry was performed at the time of enrollment. Asthma control was assessed (a) by the physician based on the Global Initiative for Asthma guidelines, (b) by the patients, and (c) by using the Asthma Control Test (ACT). Statistical analyses were done to analyze the relationships between (i) FeNO and (ii) measures of asthma control and clinical indices for asthma manifestations. Results: There was no significant difference in FeNO levels between the three groups according to levels of asthma control (controlled, partly controlled and uncontrolled) as determined by the physician (p=0.81), or by the patients (p=0.81). In addition, FeNO values were not significantly correlated with the ACT scores (r=0.031, p=0.807), while FeNO showed a correlation with peripheral blood eosinophil counts (p<0.001). Conclusion: These findings demonstrate that FeNO levels are not associated with measures of asthma control in patients treated with ICS. Information on airway inflammation from FeNO concentrations seems to be unrelated to levels of asthma control

Interferon-${\gamma}$ Enzyme-Linked Immunospot Assay in Patients with Tuberculosis and Healthy Adults

  • Kim, Cheol-Hong;Kim, Jong-Yeop;Hwang, Yong Il;Lee, Chang Youl;Choi, Jeong-Hee;Park, Yong-Bum;Jang, Seung-Hun;Woo, Heungjeong;Kim, Dong-Gyu;Lee, Myung Goo;Hyun, In-Gyu;Jung, Ki-Suck;Kim, Hyun Soo
    • Tuberculosis and Respiratory Diseases
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    • v.76 no.1
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    • pp.23-29
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    • 2014
  • Background: Interferon-${\gamma}$ assays based on tuberculosis (TB)-specific antigens have been utilized for diagnosing and ruling out latent TB and active TB, but their utility is still limited for TB incidence countries. The aim of this study is to understand the clinical utility of enzyme-linked immunospot (ELISpot) assays among patients with clinically suspected TB and healthy adults in clinical practices and community-based settings. Methods: The ELISpot assays (T SPOT.TB, Oxford Immunotec, UK) were prospectively performed in 202 patients. After excluding those with indeterminate results, 196 were included for analysis: 41 were TB patients, 93 were non-TB patients, and 62 were healthy adults. Results: The sensitivity and negative predictive values of the T SPOT.TB assays for the diagnosis of TB were 87.8% and 89.1%, respectively, among patients with suspected TB. The agreement between the tuberculin skin test (10-mm cutoff) and the T SPOT.TB assay was 66.1% (kappa=0.335) in all participants and 80.0% (kappa=0.412) in TB patients. Among those without TB (n=155), a past history of TB and fibrotic TB scar on chest X-rays were significant factors that yielded positive T SPOT.TB results. There was a significant difference in the magnitude of T SPOT.TB spot counts between TB patients and non-TB patients or healthy adults. Conclusion: The T SPOT.TB assay appeared to be a useful test for the diagnostic exclusion of TB. A positive result, however, should be cautiously interpreted for potential positives among those without active TB in intermediate TB incidence areas.

Determination of Iodine Contents in Ten kinds of Frequently used Oriental Herb Medicinal Products for Cancer Patient (암환자에게 다빈도로 활용되는 한약제제 10종에 대한 요오드의 함량 분석)

  • Lee, Chang-Hee;Choi, Jung-Eun;Kim, Sun-Ha;Chung, Yong-Sam;Moon, Jong-Hwa;Yoo, Hwa-Seung
    • Journal of Korean Traditional Oncology
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    • v.16 no.1
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    • pp.41-53
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    • 2011
  • Background and Objectives: Iodine is an essential constituent of the thyroid hormones associated with the growth and development of humans and animals as an inorganic nutrition. This element may be accumulated in human blood, tissues and body through the intake of foodstuffs, a beverage, a nutritional supplement and a medicine, among others. The aim of the research is to find out a better medicinal stuff for the thyroid cancer patient who required a low level of iodine diet. Methods: Neutron activation analysis (NAA) used for the iodine analysis is one of nuclear analytical techniques using radiation and radioisotopes and very useful as sensitive analytical technique for performing both qualitative and quantitative multi-elemental non-destructive analysis of major, minor and trace components in variety of environmental and biological materials. In this study, iodine contents in ten kinds of oriental herb medicinal products, which is frequently used to cancer patients are determined by using instrumental neutron activation analysis (INAA) at the HANARO research reactor. The samples prescribed are manufactured as powdered form for taking medicine easily. The analytical quality control is performed to assure an uncertainty of the measurement and to compensate the measured data using a biological certified reference material, NIST SRM 1572, Citrus Leaves. The measured value is $1.89{\pm}0.35mg/kg$, and the relative error is 2.88%, and relative standard deviation is 19 % due to high counting error by small counts of gamma ray spectrum. The standard deviations for other elements such as Cl, K, Mn and Na were in the range of 2 to 8%. Result: The level of iodine contents of Biki-huan, Chungryong-huan and Chungcho-huan, samples detected is less than 6 mg/kg except Hangam Plus sample (more than 210 mg/kg) and six samples were not detected. Iodine in the samples of Shoxiho-tang, Shopunghualhyl-tang, Shocungryong-tang, Banhasaxim-tang, Insampaedox-san and Myunyuk Plus were not measured, but possible level of content can be estimated from the detection limits. In addition, the concentrations of some major elements like Cl, K, Mn, Na, in the samples were determined with the detection limits. Conclusions: Most of samples showed low iodine contents of less than 6 mg/kg but it turned out that most of testing samples can be used to classify the level of iodine diet samples considering the recommended low level of iodine diet 50 ${\mu}g$/day, and a better medicinal stuff for the thyroid cancer patient can be found.

A 10-year Study of Esophageal Cancer in Guilan Province, Iran: The Guilan Cancer Registry Study (GCRS)

  • Mansour-Ghanaei, Fariborz;Heidarzadeh, Abtin;Naghipour, Mohammad Reza;Joukar, Farahnaz;Valeshabad, Ali Kord;Fallah, Mohammad-Sadegh;Rezvani, Seyed Mahmoud;Sedigh-Rahimabadi, Massih;Rokhshad, Hasan;Dadashi, Arsalan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6277-6283
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    • 2012
  • Background: Northern Iran counts as one of the highest prevalence regions for esophageal cancer (EC) worldwide. This study was designed to assess the epidemiologic aspects of EC in north central and northwest Iran over a 10 year period. Materials and Methods: The Guilan cancer registry study (GCRS) is a population-based cancer registry study featuring retrospective (1996-2003) and prospective (2004-2005) phases. A detailed questionnaire based on WHO standards for cancer registratration was applied to gather the required information. Two trained physicians coded information using ICD-O-3 in close coordination with an expert pathologist. Results: A total of 19,936 cases of malignancy (mean age $55.4{\pm}18.0$ years, range: 1-98 years) were registered, including 1,147 cases (670 males, 447 female; mean age: $64.0{\pm}11.5$ years) of EC. In 1996 the male/female ratio among patients with EC was 1.25 which increased to 1.53 in 2005. The lower third of the esophagus still remained the most common site of tumors. The average age-standardized rate (ASR) was 6.9 and 4.1 per $10^5$ men and women, respectively. In 1996, the ASRs were 7.2 and 5.2 per $10^5$ men and women which decreased to 6.9 and 4.1 per $10^5$ in 2004-2005. Squamous cell carcinoma (SCC) was the most prevalent histological subtype of EC accounting over 80% of cases. Conclusions: However the prevalence of adenocarcinoma (ADC) showed an increase to 18.4%. Guilan province may be considered a relatively low incidence region for EC.

Pretreatment Thrombocytosis as a Prognostic Factor in Women with Gynecologic Malignancies: a Meta-analysis

  • Yu, Min;Liu, Lei;Zhang, Bing-Lan;Chen, Qi;Ma, Xue-Lei;Wu, Yu-Ke;Liang, Chun-Shui;Niu, Zhi-Min;Qin, Xin;Niu, Ting
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6077-6081
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    • 2012
  • Background: This study was performed to analyze the prognostic implications of pretreatment or preoperative thrombocytosis in women with gynecologic malignancies. Material and Methods: We surveyed 2 medical databases, PubMed and EMBASE, to identified all relevant studies. A total of 14 (n=3,490) that evaluated the link between thrombocytosis and 5-year survival were included. REVMAN version 5.1 was used for our analysis and publication bias was evaluated using the Begg's funnel plot and tested by STATA 11.0. Risk ratios (RRs) with 95% confidence intervals (CIs) generated by the random effect model were used to assess the strength of any association. Results: 709(20.3%) of the 3,490 patients exhibited thrombocytosis (platelet counts > $400{\times}10^9/L$) at primary diagnosis, and their mortality was 1.62-fold higher compared with the others (RR=1.62, 95%CI=[1.28-2.05], p<0.0001). Thrombocytosis failed to have a stronger effect on the survival of advanced patients of stages III to IV in our study (n=478, RR=1.29, 95% CI=[1.13-1.48], p=0.0003), nor in women with cervical cancer in stage IB (n=1371, RR=1.73, 95% CI=[1.71-2.58], p=0.007). In addition, when adjusted for different carcinoma, it was associated with worse prognosis for all except the ones with vulvar cancer (n=201, RR=0.43, 95% CI=[0.14-1.29], p=0.13). Conclusions: This meta-analysis indicated that thrombocytosis might be associated with a worse prognosis for patients with gynecologic malignancies but without specificity or sensitivity for the ones in advanced stage. When adjusted for different gynecologic malignancies, it showed a significant effect on survival of all except vulvar cancers.

ABO Blood Group, Epstein-Barr virus Infection and Prognosis of Patients with Non-metastatic Nasopharyngeal Carcinoma

  • Zhang, Ya-Xiong;Kang, Shi-Yang;Chen, Gang;Fang, Wen-Feng;Wu, Xuan;You, Hua-Jing;He, Da-Cheng;Cao, Ya-Lin;Liang, Wen-Hua;Zhang, Li
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7459-7465
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    • 2014
  • Background: A prior study showed blood type A/AB to be associated with an increased risk of nasopharyngeal carcinoma (NPC) compared to subjects with blood type O. However, the relationship between ABO blood groups and prognosis of NPC patients is still questionable. In addition, whether Epstein-Barr virus (EBV) infection is associated with prognosis of NPC patients with different ABO blood groups is unclear. Materials and Methods: We conducted univariate and multivariable Cox regression analyses based on a consecutive cohort of 1,601 patients to investigate the above issues. Results: There was no significant difference in overall survival (OS) between different ABO blood groups (p=0.629), neither between A vs. non-A blood groups (p=0.895) nor AB vs. non-AB blood group (p=0.309) in univariate analyses and after adjusting for other factors. Interaction tests revealed that high immunoglobulin A against Epstein-Barr virus viral capsid antigen (VcA-IgA) level was associated with a favorable prognosis in male patients with UICC stage II disease who had an A blood type (p=0.008), compared with those with non-A blood type. In addition, male patients with an A blood group with a high blood lymphocyte level showeda tendency towards better survival in UICC stage III (p=0.096). Conclusions: ABO blood group status is not associated with the prognosis of patients with NPC. Additionally, blood group A male NPC patients with high VcA-IgA level or high blood lymphocyte counts might be correlated with a favorable prognosis in UICC stage II or III, respectively.

Alteration in Leukocyte Subsets and Expressions of FcγR and Complement Receptors among Female Ragpickers in Eastern India

  • Mondal, Nandan K.;Siddique, Shabana;Banerjee, Madhuchanda;Roychoudhury, Sanghita;Mukherjee, Sayali;Slaughter, Mark S.;Lahiri, Twisha;Ray, Manas R.
    • Safety and Health at Work
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    • v.8 no.2
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    • pp.198-205
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    • 2017
  • Background: There are a million ragpickers in India who gather and trade recyclable municipal solid wastes materials for a living. The objective of this study was to examine whether their occupation adversely affects their immunity. Methods: Seventy-four women ragpickers (median age, 30 years) and 65 age-matched control housemaids were enrolled. Flow cytometry was used to measure leukocyte subsets, and leukocyte expressions of $Fc{\gamma}$ receptor I (CD64), $Fc{\gamma}RIII$ (CD16), complement receptor 1 (CD35) and CR3 (CD11b/CD18), and CD14. Serum total immunoglobulin-E was estimated with enzyme-linked immunosorbent assay. Results: Compared with the controls, ragpickers had significantly (p < 0.0001) higher levels of CD8-T-cytotoxic, CD16+CD56+natural killer, and CD4+CD45RO+memory T-cells, but depleted levels of CD19+B-cells. The percentage of CD4+T-helper-cells was lower than the control group (p < 0.0001), but their absolute number was relatively unchanged (p = 0.42) due to 11% higher lymphocyte counts in ragpickers. In ragpickers, the percentages of CD14+CD16+intermediate and CD14dim CD16+nonclassical monocyte subsets were elevated with a decline in CD14+CD16-classical monocytes. The expressions of CD64, CD16, CD35, and CD11b/CD18 on both monocytes and neutrophils, and CD14 on monocytes were significantly higher in ragpickers. In addition, ragpickers had 2.7-times more serum immunoglobulin-E than the controls (p < 0.0001). After controlling potential confounders, the profession of ragpicking was positively associated with the changes. Conclusion: Ragpicking is associated with alterations in both innate (neutrophils, monocytes, and natural killer cell numbers and expression of complement and $Fc{\gamma}$ receptors) and adaptive immunity (numbers of circulating B cells, helper, cytotoxic, and memory T cells).

Uranium Enrichment Comparison of UO2 Pellet with Alpha Spectrometry and TIMS

  • Song, Ji-Yeon;Seo, Hana;Kim, Sung-Hwan;Choi, Jung-Youn
    • Journal of Radiation Protection and Research
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    • v.43 no.3
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    • pp.120-123
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    • 2018
  • Background: Analysis of enrichment of $UO_2$ is important to verify the information declared by the license-holders. The redundancy methods are required to guarantee the analysis result. Korea Institute of Nuclear Nonproliferation and Control (KINAC) used to analyze it with alpha spectrometry and consign to Korea Basic Science Institute (KBSI) Thermal Ionization Mass Spectrometry (TIMS). This article evaluated the similarity of the results with two methods and derive correlation equation. It could be compared to the results measured by TIMS running by KBSI. Materials and Methods: There are not many certified materials for the uranium enrichment value. Therefore, 34 uranium pellets, which have the wide range of uranium enrichment from 0.21 to 4.69 wt%, were used for the experiments by the alpha spectrometry and the TIMS. Results and Discussion: The study shows there are the tendency of analyzed enrichment by each equipment. It shows uranium enrichment with alpha spectrometry evaluated 17% higher than that with TIMS on average. The regression equations were also derived in case the similarity between the two results with two methods is lower than predicted. Two experiments were designed to compare the effect of number of samples. The $R^2$ was 0.9977 with 34 pellets. It shows the equation is appropriate to predict the enrichment values by TIMS with that of alpha spectrometry. The $R^2$ was 0.9858 with four pellets for ten times. The $R^2$ decreased while the number of samples increased. The discrepancy between the lowest and highest enrichment seems to be one of the reason for it. Conclusion: KINAC expects the first equation with 34 samples is useful to predict the result with TIMS, the redundancy method, based on the alpha spectrometry. The extra samples are necessary to collect if the enrichment value analyzed by TIMS is lower than the value predicted with the equation. Further study would be followed related to the impact of the peak counts for each uranium isotopes, sample amount and number of experiments when TIMS established in KINAC by the end of 2018.

Studies on Scintillation Proximity Assay for the mesurement of alpha-hCG (Alpha-hCG 측정을 위한 섬광 근접 측정법 (Scintillation Proximity Assay)에 관한 연구)

  • Choi, Tae-Hyun;Lim, Sang-Moo;Choi, Chang-Woon;Chung, Wee-Sup;Lim, Soo-Jeong;Lee, Su-Jin;Lee, Tae-Sup;Awh, Ok-Doo
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.2
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    • pp.133-139
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    • 2002
  • Purpose: Scintillation Proximity Assay (SPA) does not require the physical separation of receptor bound form from free form. SPA was applied to the study of interaction of human chorionic gonadotropin (hCG) and $anti-{\alpha}$ hCG in serum. Materials and methods: $Anti-{\alpha}$ hCG was biotinylated for the binding to streptavidin. The assay was based on the simple competitive binding method between $[^{125}I]hCG$ and the hCG in sample serum, with $anti-{\alpha}$ hCG-coated beads. Aliquots of biotinylated $anti-{\alpha}$ hCG were dispensed into scintillation vials containing $100{\mu}{\ell}\;[^125}I]hCG\;and\;200{\mu}{\ell}$ of either a standard concentration of hCG for preparation of standard curve or unknown sample, and incubated for 20 min. at room temperature. Then $20{\mu}{\ell}$ streptavidin-coated beads were added to vials, and finally incubated for 10 min at room temperature. Values for unknown samples were then calculated from the standard curve. Results: Optimal background counts were certificated using varied radioactivity of radionuclides. Appropriate standard curve was obtained from SPA method successively, and the concentration of hCG from unknown serum was determined by standard curve. The result from SPA assay was similar to that of RIA. Conclusion: This observation confirms that SPA method could be useful for clinical diagnosis.