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Mechanism of Glucose Uptake on PMA Stimulated Neutrophils (PMA에 의한 중성구의 당섭취 기전 연구)

  • Paik, Jin-Young;Ko, Bong-Ho;Yoo, Man-Kil;Jin, Kwang-Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.39 no.3
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    • pp.249-255
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    • 2007
  • While respiratory burst enhances neutrophil glucose utilization, many neutrophil functions are critically influenced by extracellular matrix interaction and phosphoinositide-3-OH kinase (PI3K) signaling. We thus evaluated the role of RGD integrin occupancy and PI3K inhibition on respiratory burst and [18F]FDG uptake of stimulated neutrophils. Human neutrophils were stimulated by 100 ng/mL phorbol-myristate-acetate (PMA), and respiratory burst was measured by cumulative luminescence with lucigenin. [18F]FDG uptake and total hexokinase activity was measured 20 min after PMA stimulation in the presence or absence of soluble RGD peptides (200 g/mL) and/or the PI3K inhibitor wortmannin (200 nM). PMA induced a 71.70.9 fold increase in neutrophil oxygen intermediate generation. [18F]FDG uptake was increased to $194.6{\pm} 3.7%$ and hexokinase activity to $145.0{\pm}2.0%$ of basal levels (both p<0.0005). RGD peptides attenuated respiratory burst activation to $35.6{\pm}0.2%$ (p<0.005), but did not inhibit stimulated [18F]FDG uptake or hexokinase activity. In contrast, without affecting respiratory burst activation, wortmannin inhibited PMA stimulated [18F]FDG uptake to $66.9{\pm}1.6%$ and hexokinase activity to $81.0{\pm}4.2%$ (both P<0.0005), demonstrating its dependence on PI3K activity. Neither RGD nor wortmannin reversed the other's inhibitory effect on stimulated [18F]FDG uptake and hexokinase activity or respiratory burst, which suggests the involvement of distinct signaling pathways. Neutrophil [18F]FDG uptake is enhanced by PMA through a mechanism that requires PI3K activity but is independent of integrin receptor occupancy or respiratory burst activation.

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L-NAME Inhibits Hyperalgesia Induced by Freund's Complete Adjuvant in Rat Paw (L-NAME에 의한 쥐의 발바닥에서 Freund's Complete Adjuvant에 의해 유발된 통증 억제)

  • Lee, Cheong;Choi, Yoon;Song, Myung-Hee;Leem, Joong-Woo;Lee, Dong-Myung;Raja, Srinivasa N.
    • The Korean Journal of Pain
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    • v.11 no.2
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    • pp.194-200
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    • 1998
  • Background: Effect of nitric oxide on the hyperalgesia induced by inflammation is controversial. We attempted to find out the peripheral effects of nitric oxide (NO) on hyperalgesia induced by Freund's complete adjuvant (FCA) induced inflammation. Methods: Male Sprague Dawley rats were divided into three groups; control, low dose NG-nitro-L-arginine methyl ester (L-NAME, 500 ug), high dose L-NAME (5 mg). Inflammation was induced by injecting 0.1 ml of FCA intraplantarly, which shows typical hyperalgesia within twelve hours after injection and maintained for about one week. Drugs were injected 2 hours before, just before, and 3, 6, 9, 12 hours after the injection of FCA. Effect of L-NAME on hyperalgesia was assessed by measuring mechanical hyperalgesia and spontaneous pain for 3 days. Results: When injected at the site of inflammation, L-NAME caused dose dependent reduction of spontaneous hyperalgesia. Mechanical hyperalgesia was also reduced by high dose L-NAME (p<0.05). After systemic injection of high dose L-NAME in the back, no significant difference was noticed. Conclusions: This suggest that L-NAME reduces FCA induced hyperalgesia via peripheral action.

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Comparison of Decision System in both Differentiation of Syndromes and Treatments(辨證論治) and Divination by Achillea sibirica(蓍草占) (변증논치(辨證論治)와 시초점(蓍草占)의 의사결정(意思決定) 체계(體系) 비교)

  • Jo, Hak-Jun
    • Journal of Korean Medical classics
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    • v.25 no.4
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    • pp.39-55
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    • 2012
  • Objective : In order to find the decision system in differentiation of syndromes and treatments, I paid attention to divination by Achillea sibireca. Method : I pulled out the elements of differentiation of syndromes and treatments in Zh$\bar{o}$ng y$\bar{i}$n$\grave{e}$i k$\bar{e}$ xu$\acute{e}$(中醫內科學), Uihagipmun Sanghan(醫學入門 傷寒), Donguibogam Japbyeong(東醫寶鑑 雜病) and compared them with the horoscope in The Book of Changes(周易) from the relativity of both eight principles(八綱) etc and subdivision in the entity of the cosmos (太極內 分化). Result : From this viewpoint, the decision system that has relative references in differentiation of syndromes & treatments on cold diseases(傷寒病) and complexed diseases(雜病) by eight principles etc can be compared with the decision system in divination by Achillea sibireca that the entity of the cosmos(太極) gradually can be breakdown into the positive and negative(陰陽), the positive and negative can be breakdown into four phases(四象), four phases can be breakdown into eight signs of divination(八卦), eight signs of divination can be breakdown into 64 divination signs(64卦). Conclusion : I had found that differentiation of syndromes and treatments and divination by Achillea sibireca have similarity to each other in side of decision system. Those decision systems for clinical use and telling the future has many relative references and are made of multiple structures. Clinician can easily, exactly distinguish similar syndromes of many another diseases through this way.

Clinical Prognostic Factors and Survival Outcome in Renal Cell Carcinoma Patients - A Malaysian Single Centre Perspective

  • Yap, Ning Yi;Ng, Keng Lim;Ong, Teng Aik;Pailoor, Jayalakshmi;Gobe, Glenda Carolyn;Ooi, Chong Chien;Razack, Azed Hassan;Dublin, Norman;Morais, Christudas;Rajandram, Retnagowri
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7497-7500
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    • 2013
  • Background: This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms. Materials and Methods: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis. Results: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, $9.5{\pm}4.3cm$, was larger than non palpable masses, $5.3{\pm}2.7cm$ (p<0.001). Conclusions: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.

Purification and Characterization of a Laccase from the Edible Wild Mushroom Tricholoma mongolicum

  • Li, Miao;Zhang, Guoqing;Wang, Hexiang;Ng, Tzibun
    • Journal of Microbiology and Biotechnology
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    • v.20 no.7
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    • pp.1069-1076
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    • 2010
  • A novel laccase from Tricholoma mongolicum was purified by using a procedure that entailed ion-exchange chromatographies on DEAE-cellulose, CM-cellulose, and Q-Sepharose, and FPLC-gel filtration on Superdex 75. The purified enzyme was obtained with a specific activity of 1,480 U/mg-protein and a final yield of 15%. It was found to be a monomeric protein with a molecular mass of 66 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its N-terminal amino acid sequence was GIGPVADLYVGNRIL, similar to some but also different to other mushroom laccases. The optimum pH and temperature for the purified enzyme were pH 2 to pH 3 and $30^{\circ}C$, respectively. It displayed a low $K_m$ toward 2,7-azinobis (3-ethylbenzothiazolone-6-sulfonic acid) diammonium salt (ABTS) and high $k_{cat}/K_m$ values. The purified laccase oxidized a wide range of lignin-related phenols, but exerted maximal activity on ABTS. It was significantly inhibited by $Hg^{2+}$ ions, and remarkably stimulated by $Cu^{2+}$ ions. It inhibited HIV-1 reverse transcriptase and proliferation of hepatoma HepG2 cells and breast cancer MCF7 cells with an $IC_{50}$ of 0.65 ${\mu}M$, 1.4 ${\mu}M$, and 4.2 ${\mu}M$, respectively, indicating that it is also an antipathogenic protein.

Relationship between 25-hydroxyvitamin D and metabolic syndrome among Jordanian adults

  • Khader, Yousef S.;Batieha, Anwar;Jaddou, Hashim;Batieha, Zahi;El-Khateeb, Mohammed;Ajlouni, Kamel
    • Nutrition Research and Practice
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    • v.5 no.2
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    • pp.132-139
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    • 2011
  • Evidence of the association between 25-hydroxyvitamin D (25(OH)D) and metabolic syndrome (MeS) remains uncertain and incongruent. This study aimed to determine the association between 25(OH)D and MeS among Jordanian adults. A complex multistage sampling technique was used to select a national population-based household sample. The present report deals exclusively with adults aged > 18 years who had complete information on all components of MeS (n = 3,234). A structured questionnaire was used to collect all relevant information. Anthropometric, clinical, and laboratory measurements were obtained. MeS was defined according to the International Diabetes Federation (IDF) definition. Of the total, 42.0% had MeS and 31.7% had 25(OH)D < 30 ng/ml. In a stratified analysis, the prevalence of MeS did not differ significantly between subjects with low and normal 25(OH)D levels for men and women in all age groups. In the multivariate analysis, the odds of MeS were not significantly different between subjects with low and normal 25(OH)D levels (OR = 0.85, 95% CI: 0.70, 1.05, P-value = 0.133). The association between 25(OH)D and MeS remained non-significant when 25(OH)D was analyzed as a continuous variable (OR = 1.004, 95% CI; 1.000, 1.008, P = 0.057) and when analyzed based on quartiles. None of the individual components of MeS were significantly associated with 25(OH)D level. This study does not provide evidence to support the association between 25(OH)D level and MeS or its individual components. Prospective studies are necessary to better determine the roles of 25(OH)D levels in the etiology of MeS.

Effects of Bangkeehwangkee-tang ($f{\acute{a}}ngj{\check{i}}hu{\acute{a}}ngq{\acute{i}}-t{\bar{a}}ng$) Treatment on the Monosodium Iodoacetate-induced Osteoarthritis in Rats (방기황기탕이 Monosodium Iodoacetate로 유발된 흰쥐의 골관절염에 미치는 영향)

  • Kim, Dae-Hun;Kang, Sung-In;Song, Min-Yeong;Choi, Jin-Bong;Bae, Kil-Joon;Han, Jeong-Seok;Yang, Mi-Sung;Sin, Yong-Jeen
    • Journal of Korean Medicine Rehabilitation
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    • v.24 no.2
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    • pp.15-29
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    • 2014
  • Objectives We have studied to know effects of Bangkeehwangkee-tang on the monosodium iodoacetate (MIA) induced osteoarthritis in rats. Methods Osteoarthritis was induced by injection of monosodium iodoacetate into knee joint cavity of rats. Rats are devided into 4 groups; Sham, control, Bangkeehwangkee-tang, Shinbaro. Sham group was injected by normal saline into knee joint cavity only. Control group was taken no treatment and Experimental groups were taken extracts of Bangkeehwangkee-tang and Shinbaro by orally once a day for 4 weeks. The content of TNF-$\alpha$, IL- $1{\beta}$ and IL-6 in synovial fluids were analysed. COX-2 in chondrocytes and blood PGE2 concentration were analysed. Histopathological examination was performed by Safranin-O fast green staining and Mankins score checking. Results The content of TNF-$\alpha$, IL-$1{\beta}$ in experimental groups were decreased compared with control group. COX-2 in chondrocytes and blood PGE2 concentration in experimental groups were decreased compared with control group. Histopathologically, osteoarthritic scores of experimental groups were decreased compared with control group. But the content of IL-6 in synovial fluids was not significantly compared with control group. Conclusions According to these results, it can be suggested that Bangkeehwangkee-tang has anti-arthritic effects on the MIA induced osteoarthritis in rats.

A Study on Variables Related to Paternal Parenting Behavior : Father Involvement, Parenting Stress, and Parenting Self-efficacy (아버지 양육행동에 영향을 미치는 양육참여, 양육스트레스, 양육효능감의 상대적 영향력 탐색)

  • Kim, Ga Yun;Shin, Hae Young
    • Korean Journal of Childcare and Education
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    • v.9 no.2
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    • pp.191-213
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    • 2013
  • The purpose of this study was to examine the relationship pattern among paternal parenting behaviors, father involvement, parenting stress, and parenting self- efficacy. The subjects were 299 fathers of 3 to 4 year-old children at 2 child care centers and 11 kindergartens in Seoul and the Gyunggi-do area. Fathers responded to a modified version of Parenting Daily Hassles(Crinc & Greeberg, 1990), a re vised version of Parenting Sense of Competence(Gibaud-Wallston & Wandersman, 1978), and questionnaires including questions about parenting behaviors(Park, 2000) and father involvement developed by authors. Stepwise regression analyses showed that fathers' cognitive efficacy of parenting and the frequency of play involvement on weekdays significantly explained paternal 'warmth encouragement'. Also, cognitive efficacy and the frequency and time amount of play involvement on weekdays significantly explained paternal 'setting up the limitations'. Meanwhile, fathers' emotional efficacy and the amount of play time involvement on weekdays significantly explained paternal 'over-protection permission'. Finally, the cognitive and emotional efficacy of rearing and parenting stress significantly explained paternal 'rejection non-intervention'.

Experimental Study for Effect of Banhasasim-tang on Mice with Reflux Esophagitis (역류성 식도염 유발 생쥐의 반하사심탕(半夏瀉心湯)투여 효과에 대한 실험 연구)

  • Jang, Myeong-Woong;Lim, Seong-Woo
    • The Journal of Internal Korean Medicine
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    • v.34 no.4
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    • pp.362-374
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    • 2013
  • Objectives : This study was carried out to investigate the inhibitory effect of Banhasasim-tang on early reflux esophagitis by control of gastric peristalsis and the lower esophageal sphincter in mice. Methods : Experimental mice were classified into three groups. The normal group were mice with no inflammation. The control group were mice with gastroesophageal reflux elicited by alcohol. The sample group were mice administered Banhasasim-tang after gastroesophageal reflux elicitation. We observed morphological change and production of ghrelin, substance P, and inducible nitric oxide synthase (iNOS) in gastroesophageal junction mucosa. In addition, we examined change of epithelial junction in esophageal mucosa and change of lower esophageal sphincter distribution. Results : The migration of inflammation-related cells in lamina propria of gastroesophageal junction decreased more in the sample group than in the control group. The positive reaction of ghrelin, substance P, and iNOS significantly decreased more in the sample group than in the control group (p<0.05). Injury of the epithelial junction in the esophageal mucosa and outer oblique layer in the lower esophageal sphincter were significantly mitigated by Banhasasim-tang administration in the sample group (p<0.05). Conclusions : According to the above results, it is supposed that Banhasasim-tang inhibits early reflux esophagitis by controlling not only gastric peristalsis and acid secretion through ghrelin, and substance P but also the lower esophageal sphincter through iNOS.

Roles of Ki67 in Breast Cancer - Important for Management?

  • Yip, CH;Bhoo-Pathy, N;Daniel, JM;Foo, YC;Mohamed, AK;Abdullah, MM;Ng, YS;Yap, BK;Pathmanathan, R
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1077-1082
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    • 2016
  • Background: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer. Materials and Methods: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22. Results: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy. Conclusions: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.