• Title/Summary/Keyword: molecular therapy

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Naringin Protects Ovalbumin-induced Asthma through the Down-regulation of MMP-9 Activity and GATA-3 Gene (Naringin에 의한 천식치료 효과연구)

  • Lee, Chang-Min;Chang, Jeong-Hyun;Jung, In-Duk;Jeong, Young-Il;Tae, Noh-Kyung;Park, Hee-Ju;Kim, Jong-Suk;Shin, Yong-Kyoo;Park, Sung-Nam;Park, Yeong-Min
    • Journal of Life Science
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    • v.19 no.6
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    • pp.735-743
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    • 2009
  • The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.

Pathogens and Prognotic Factors for Early Onset Sepsis in Very Low Birth Weight Infants (극소 저체중 출생아에서 조기 패혈증의 원인균과 예후인자)

  • Kim, Yi-Sun;Kim, Jin-Kyu;Yoo, Hye-Soo;Ahn, So-Yoon;Seo, Hyun-Ju;Choi, Seo-Heui;Park, Soo-Kyung;Jung, Yu-Jin;Kim, Myo-Jing;Jeon, Ga-Won;Koo, Soo-Hyun;Lee, Kyung-Hoon;Chang, Yun-Sil;Park, Won-Soon
    • Neonatal Medicine
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    • v.16 no.2
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    • pp.163-171
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    • 2009
  • Purpose: This study was conducted to determine the incidence, causative pathogens, risk factors and mortality for early onset sepsis in the first three days in very low birth weight infants. Methods: The medical records of 1,124 very low birth weight infants admitted to the neonatal intensive care unit of Samsung Medical Center between November 1994 and December 2008 were retrospectively reviewed. The incidence, causative pathogens, risk factors, and mortality for early onset sepsis in the first 3 days of life in very low birth weight infants were evaluated. Results: Early onset sepsis, as confirmed by positive blood cultures, was present in 17 of 1,124 infants (1.5%). Sixty-four percent of the isolated pathogens were gram-positive bacteria and 35% of the isolated pathogens were gram-negative bacteria. The dominant pathogens of early onset sepsis included Staphylococcus aureus (23.5%), Esherichia coli (23.5%), and Enterococcus (17.6%). Vaginal delivery (adjusted odds ratio [OR], 3.7; 95% confidence interval [CI], 1.3-10.3; P=0.01) was associated with early onset sepsis. The overall mortality (adjusted hazard ratio, 3.0; 95% CI, 1.4-6.5; adjusted P=0.0039) and mortality within 72 hours of life (adjusted hazard ratio, 6.5; 95% CI, 2.2-18.9; adjusted P=0.0005) of infants with early onset sepsis were higher than that of uninfected infants. Conclusion: Early onset sepsis remains an uncommon, but potentially lethal problem among very low birth weight infants. Knowledge of the likely causative organisms and risk factors for early onset sepsis can aid in instituting prompt and appropriate therapy, in order to minimize mortality.

Usefulness of $^{18}F$-FDG PET/CT in Locoregional Recurrence of Differentiated Thyroid Cancer: Comparison PET/CT to PET and Neck Ultrasonography for Biopsy-proven Lesions (갑상선유두암 재발 진단에서 $^{18}F$-FDG PET/CT와 경부초음파검사 병용의 유용성: PET, 경부초음파검사 그리고 혈청 티로글로불린 (thyroglobulin)의 비교)

  • Kim, Kun-Ho;Shong, Min-Ho;Seo, Young-Duk;Kim, Seong-Min
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.5
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    • pp.411-420
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    • 2009
  • Purpose: The aim of this study was to investigate the usefulness of $^{18}F$-FDG PET/CT with neck ultrasonography (neck US) in patients with recurrent, papillary thyroid cancer. Material and methods: This retrospective study (December 2006 to April 2008) enrolled sixty-one patients (ninety-one lesions) who underwent high-dose $^{131}I$-ablation therapy after total thyroidectomy, and evaluated recurred papillary thyroid cancer. All lesions were confirmed by histopathology and compared histopathologic findings to PET, PET/CT, and neck US findings. Results: In sixty-one patients (57 women, 4 men; age range, 24-81 years, mean 49 years; 61 papillary carcinomas), the sensitivity, specificity, accuracy of $^{18}F$-FDG PET/CT was 87.2%, 64.0%, 78.1% on a patient basis and 92.3%, 66.7%, 80.9% on a lesion basis, respectively. The sensitivity, specificity, accuracy of $^{18}F$-FDG PET was 71.8% (p=0.03), 59.0% (p=1.00), 67.2% (p=0.03) on a patient basis and 78.8% (p<0.01), 64.1% (p=1.00), 72.5% (p=0.02) on a lesion basis, respectively. The sensitivity, specificity, accuracy of neck US was 71.1% (p=0.07), 52.2% (p=0.75), 63.9% (p=0.05) on a patient basis and 71.2% (p<0.01), 61.5% (p=1.00), 67.0% (p=0.06) on a lesion basis, respectively. Combined $^{18}F$-FDG PET/CT with neck US improved the sensitivity, specificity, accuracy to 94.7% (p=0.50), 82.6% (p=0.13), 90.2% (p=0.03) on a patient basis and 96.2% (p=0.50), 89.7% (p<0.01), 93.4% (p<0.01) on a lesion basis, respectively. Conclusion: $^{18}F$-FDG PET/CT demonstrated significantly higher sensitivity than neck US for the detection of recurred papillary thyroid cancer lesions. Furthermore, combined $^{18}F$-FDG PET/CT with neck US showed more improved sensitivity, specificity, accuracy for diagnosis of recurrent papillary thyroid cancer.

The Significance of Ku70 Expression in Patients with Nasopharyngeal Carcinoma (비인강암에서 방사선치료의 예측인자로써 Ku70 발현의 의의)

  • Song Si Yeol;Lee Sang-wook;Yu Eunsil;Cho Kyung-Ja;Park Jin-hong;Kim Sang Yoon;Nam Soon Yuhl;Lee Bong-Jae;Kim Sung Bae;Choi Seung-Ho;Ahn Seung Do;Shin Seong Soo;Choi Eun Kyung
    • Radiation Oncology Journal
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    • v.23 no.1
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    • pp.1-8
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    • 2005
  • Purpose : The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-PKcs, influence the response to radiotherapy (RT) and outcome of treatment of non-disseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. Materials and Methods : Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The over-expression of Ku70 or DNA-PKcs groups Included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were peformed to determine the prognostic factors that influenced locoregional control of NPC. Results : The five-year locoregional control rate was significantly higher in the low Ku70 group (Ku(-)) (85%) than in the high Ku70 group (Ku(+)) (42%) (p=0.0042). However, there were no differences in the metastases-free survival rates between the two groups (Ku70 (+), 82%; Ku70 (-), 78%; p=0.8672). Univariate analysis indicated that the over-expression of Ku70 surpassed other well-known predictive clinocopathologic parameters as an Independent prognostic factor for locoregionai control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an over-expression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. Conclusion : Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with non-disseminated NPC.

An Investigation of Glyceollin I's Inhibitory Effect on The Mammalian Adenylyl (글리세올린 I의 아데니닐 고리화 효소 활성 억제 효능과 결합 부위 비교 분석)

  • Kim, Dong-Chan;Kim, Nam Doo;Kim, Sung In;Jang, Chul-Soo;Kweon, Chang Oh;Kim, Byung Weon;Ryu, Jae-Ki;Kim, Hyun-Kyung;Lee, Suk Jun;Lee, Seungho;Kim, Dongjin
    • Journal of Life Science
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    • v.23 no.5
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    • pp.609-615
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    • 2013
  • Glyceollin I has gained attention as a useful therapy for various dermatological diseases. However, the binding property of glyceollin I to the mammalian adenylyl cyclase (hereafter mAC), a critical target enzyme for the down-regulation of skin melanogenesis, has not been fully explored. To clarify the action mechanism between glyceollin I and mAC, we first investigated the molecular docking property of glyceollin I to mAC and compared with that of SQ22,536, a well-known mAC inhibitor, to mAC. Glyceollin I showed superiority by forming three hydrogen bonds with Asp 1018, Trp 1020, and Asn 1025, which exist in the catalytic site of mAC. However, SQ22,536 formed only two hydrogen bonds with Asp 1018 and Asn 1025. Secondly, we confirmed that glyceollin I effectively inhibits the formation of forskolin-induced cAMP and the phosphorylation of PKA from a cell-based assay. Long term treatment with glyceollin I had little effect on the cell viability. The findings of the present study also suggest that glyceollin I may be extended to be used as an effective inhibitor of hyperpigmentation.

The Role of the Endometrium and Embryo in Human Implantation (인간 착상 과정에 자궁내막과 배아의 역할)

  • Jee, Byung-Chul
    • Development and Reproduction
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    • v.13 no.1
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    • pp.1-11
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    • 2009
  • Implantation itself is governed by an array of endocrine, paracrine and autocrine modulators, of embryonic and maternal origin. Window of implantation is the unique temporal and spatial expression of factors allows the embryo to implant via signaling, appositioning, attachment, and invasion in a specific time frame of $2{\sim}4$ days. When the embryo has arrived in the uterine cavity, a preprogrammed sequence of events occurs, which involves the production and secretion of a multitude of biochemical factors such as cytokines, growth factors, and adhesion molecules by the endometrium and the embryo, thus leading to the formation of a receptive endometrium. Cytokines such as LIF, CSF-1, and IL-1 have all been shown to play important roles in the cascade of events that leads to implantation. Integrin, L-selectin ligands, glycodelin, mucin-1, HB-EGF and pinopodes are involved in appositioning and attachment. The embryo also produces cytokines and growth factors (ILs, VEGF) and receptors for endometrial signals such as LIF, CSF-1, IGF and HB-EGF. The immune system and angiogenesis play an important role. The usefulness of these factors to assess endometrial receptivity and to estimate the prognosis for pregnancy in natural and artificial cycles remains to be proven. Integrins, pinopodes, glycodelin and LIF (from biopsies) are promising candidates; from uterine flushings, glycodelin and LIF are also candidates. The ideal serum marker is not available, but VEGF, glycodelin and CSF have some clinical implications. Further evaluation that includes larger groups of infertile women and fertile controls are needed to elucidate whether their presence in plasma, flushing fluid, or endometrial samples can be used as some kind of a screening tool to assess endometrial function and prognosis for pregnancy before and after artificial reproductive therapy. A better understanding of their function in human implantation may lead to therapeutic intervention, thereby improving the success rate in reproduction treatment. New molecular techniques are becoming available for measuring both embryonic and endometrial changes prior to and during implantation. The use of predictive sets of markers may prove to be more reliable than a single marker. Ultimately, the aim is to use these tools to increase implantation in artificial cycles and consequently improve live-birth rates.

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Expression of Cell Cycle Related Genes in HL60 Cells Undergoing Apoptosis by X-irradiation (HL60 세포주에서 방사선 조사에 의한 Apoptosis와 세포 주기 관련 유전자의 발현 변화)

  • Kim, Jin-Hee;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.16 no.4
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    • pp.377-388
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    • 1998
  • Purpose : To evaluate changes in expression of cell cycle related genes during apoptosis induced in HL60 cells by X-irradiation to understand molecular biologic aspects in mechanism of radiation therapy. Material and Methods : HL-60 cell line (promyelocytic leukemia cell line) was grown in culture media and irradiated with 8 Gr by linear accelerator (6 MV X-ray). At various times after irradiation, ranging from 3 to 48 hours were analyzed apoptotic DNA fragmentation assay for apoptosis and by western blot analysis and semi-quantitative RT-PCR for expression of cell cycle related genes (cyclin A, cyclin B, cyclin C, cyclin Dl, cyclin E, cdc2, CDK2, CDK4, $p16^{INK4a}$, $p21^{WAF1}$, $p27^{KIP1}$, E2F, PCNA and Rb). Results : X-irradiation (8 Gy) induced apoptosis in HL-60 cell line. Cycline A protein increased after reaching its peak 48 h after radiation delivery and cyclin E, E2F, CDK2 and RB protein increased then decreased after radiation. Radiation induced up-regulation of the expression of E2F is due to mostly increase of Phosphorylated retinoblastoma proteins (ppRb). Cyclin Dl, PCNA, CDC2, CDK4 and $p16^{INK4a}$ protein underwent no significant change at any times after irradiation. There was not detected $p21^{WAF1}$ and $p27^{KIP1}$ protein. Cyclin A, B, C mRNA decreased immediately after radiation and then increased at 12 h after radiation. Cyclin Dl mRNA increased immediately and then decreased at 48 h after radiation. After radiation, cyclin E mRNA decreased with the lapse of time. CDK2 mRNA decreased at 3h and increased at eh after radiation. CDK4 mRNA rapidly increased at 6 to 12 h after radiation. There was no change of expression of $p16^{INK4a}$ and not detected in expressin of $p21^{WAF1}$ and $p27^{KIP1}$ mRNA. Conclusion : We suggest that entry into S phase may contribute to apoptosis of HL60 cells induced by irradiation. Increase of ppRb and decrease of pRb protein are related with radiation induced auoptosis of HL60 cells and tosis of HL60 cells induced by irradiation. Increase of ppRb and decrease of PRb protein are related with radiation induced apoptosis of HL60 cells and this may be associated with induction of E2F and cyclinE/CDK2. These results support that $p21^{WAF1}$ and $p27^{KIP1}$ are not related with radiation induced-apoptosis.

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Classification of submitted KSNMT dissertation (대한핵의학기술학회 투고 논문 분류)

  • Han, Dong-Chan;Lee, Hyuk;Hong, Gun-Chul;Ahn, Byeong-Ho;Choi, Seong-Wook
    • The Korean Journal of Nuclear Medicine Technology
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    • v.21 no.1
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    • pp.65-69
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    • 2017
  • Purpose KSNMT(Korea Society of Nuclear Medicine Technology) stepping first step in 1997, has published first journal related with nuclear medicine technology in 1985. With classifying In Vivo Session Dissertation reported in the entire journal, trend of the Dissertation will be studied. Materials and Methods Dissertations which published from 1985 to first half of 2016 in the journal are classified with presentation form and with scanner, And all the data is organized with Excel program. Through the data, the number of dissertations published in each year, the number of dissertation published in details, and keyword distributions in each period are analyzed. Results The number of In-vivo section dissertations was 1151 and the number of In-vivo section dissertations that have common subject with In-vitro section was 28. The number of In-vivo section dissertation in 1980s was 46, in 1990s was 149, in 2000 was 467 and from 2010 to the first half of 2016 was 517. The number of dissertation with original articles was 571, with abstract was 529, with symposium was 31, with special lecture was 25, with review was 11, with interesting image was 7, with poster was 3 and with case report was 2. With symposium and special lecture excluded, which count 56, the number of dissertation with PET was 319, with Planar was 302, with SPECT was 172, with radiopharmaceutical was 113, with guard and safety management 103, with BMD was 28, etc. was 86. The number of dissertation about oncology was 201, about scanner was 179, about cardiovascular and circulatory system was 102, about safe environment was 82, about musculoskeletal system was 76, about nervous nuclear medicine was 66, about quality assurance was 61, about genitourinary system was 56, about endocrine system was 49, about digestive system was 44, about Therapy, about industrial safety was 24, about molecular imaging was 15, infection and inflammation was 9, about respiratory system was 8 and etc. was 108. The mostly used keyword through 1999 to 2005 was PET and through 2006 to 2016 was PET/CT. Conclusion To encourage various dissertations to be submitted, Korea Society of Nuclear Medicine should analyze date about not only about dissertations that are already published, but also about various research materials. Moreover, Korea Society of Nuclear Medicine also have to provide technical support such as sharing big data from homepage and systematical support to its member to publish dissertation that has high impact factor. It is important each individual researcher to have continuing effort as well as each organization cooperation.

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Analysis of HBeAg and HBV DNA Detection in Hepatitis B Patients Treated with Antiviral Therapy (항 바이러스 치료중인 B형 간염환자에서 HBeAg 및 HBV DNA 검출에 관한 분석)

  • Cheon, Jun Hong;Chae, Hong Ju;Park, Mi Sun;Lim, Soo Yeon;Yoo, Seon Hee;Lee, Sun Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.23 no.1
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    • pp.35-39
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    • 2019
  • Purpose Hepatitis B virus (hepatitis B virus, HBV) infection is a worldwide major public health problem and it is known as a major cause of chronic hepatitis, liver cirrhosis and liver cancer. And serologic tests of hepatitis B virus is essential for diagnosing and treating these diseases. In addition, with the development of molecular diagnostics, the detection of HBV DNA in serum diagnoses HBV infection and is recognized as an important indicator for the antiviral agent treatment response assessment. We performed HBeAg assay using Immunoradiometric assay (IRMA) and Chemiluminescent Microparticle Immunoassay (CMIA) in hepatitis B patients treated with antiviral agents. The detection rate of HBV DNA in serum was measured and compared by RT-PCR (Real Time - Polymerase Chain Reaction) method Materials and Methods HBeAg serum examination and HBV DNA quantification test were conducted on 270 hepatitis B patients undergoing anti-virus treatment after diagnosis of hepatitis B virus infection. Two serologic tests (IRMA, CMIA) with different detection principles were applied for the HBeAg serum test. Serum HBV DNA was quantitatively measured by real-time polymerase chain reaction (RT-PCR) using the Abbott m2000 System. Results The detection rate of HBeAg was 24.1% (65/270) for IRMA and 82.2% (222/270) for CMIA. Detection rate of serum HBV DNA by real-time RT-PCR is 29.3% (79/270). The measured amount of serum HBV DNA concentration is $4.8{\times}10^7{\pm}1.9{\times}10^8IU/mL$($mean{\pm}SD$). The minimum value is 16IU/mL, the maximum value is $1.0{\times}10^9IU/mL$, and the reference value for quantitative detection limit is 15IU/mL. The detection rates and concentrations of HBV DNA by group according to the results of HBeAg serological (IRMA, CMIA)tests were as follows. 1) Group I (IRMA negative, CMIA positive, N = 169), HBV DNA detection rate of 17.7% (30/169), $6.8{\times}10^5{\pm}1.9{\times}10^6IU/mL$ 2) Group II (IRMA positive, CMIA positive, N = 53), HBV DNA detection rate 62.3% (33/53), $1.1{\times}10^8{\pm}2.8{\times}10^8IU/mL$ 3) Group III (IRMA negative, CMIA negative, N = 36), HBV DNA detection rate 36.1% (13/36), $3.0{\times}10^5{\pm}1.1{\times}10^6IU/mL$ 4) Group IV(IRMA positive, CMIA negative, N = 12), HBV DNA detection rate 25% (3/12), $1.3{\times}10^3{\pm}1.1{\times}10^3IU/mL$ Conclusion HBeAg detection rate according to the serological test showed a large difference. This difference is considered for a number of reasons such as characteristics of the Ab used for assay kit and epitope, HBV of genotype. Detection rate and the concentration of the group-specific HBV DNA classified serologic results confirmed the high detection rate and the concentration in Group II (IRMA-positive, CMIA positive, N = 53).