• Title/Summary/Keyword: human-to-human (H2H)

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Differential Diagnosis of Chemical-induced Hepatobiliary Toxicities Using a New Hepatobiliary Imaging Agent in Mice

  • Ryu, Chong-Kun;Pie, Jae-Eun;Choe, Jae-Gol;Cheon, Joon;Sohn, Jeong-Won;Jurgen Seidel;David S. Paik;Michael V. Green;Chang H. Paik;Kim, Meyoung-Kon
    • Environmental Mutagens and Carcinogens
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    • v.21 no.1
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    • pp.1-8
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    • 2001
  • We have synthesized $^{99m}$Tc-mercaptoacetyltriglycine (MAG3)-biocytin as a new imaging agent for hepatobiliary scintigraphy. The aim of this study was to evaluate the usefulness of $^{99m}$Tc-MAG3-biocytin scintigraphy in differentiating carbon tetrachloride ( $CCl_4$)-induced hepatotoxicity from $\alpha$-naphthylisothiocyanate (ANIT)-induced cholestasis in mice, which reflecting the differential diagnosis of neonatal jaundice caused by neonatal hepatitis from congenital biliary atresia in humans. Methods: Balb/c mice (female, 20 g, n=4-6) were pretreated with $CCl_4$(0.5 or $1.0m\ell$/kg) and ANIT ($150 or 300 m\ell$/kg) 18 h before scintigraphy. Biochemical and histopathological examinations showed a pattern of typical acute hepatitis (increase of transaminases and hepatocellular necnsis) in $CCl_4$-treated mice and cholestasis (increase of alkaline phosphatase and ${\gamma}$-glutamyltransferase, and biliary hyperplasia) in ANIT-treated mice, respectively, Mice were fasted at least 4 hr prior to the intravenous injection of $^{99m}$Tc-MAG3-biocytin (18.5 MBq/20$\mu\textrm{g}$) in 2% human serum albumin in saline. Scintigraphy was performed with a ${\gamma}$-camera equipped with a 1-mm diameter pin-hole collimator for 30 min and images were acquired every 15 s. We compared the values of physical parameters, such as peak liver/heart ratio ($${\gamma}$_{max}$) and peak ratio time ($t_{max}$) far $^{99m}$Tc-MAG3-biocytin scintigraphy. Results: Scintigraphic parameters of the $CCl_4$-pretreated (0.5 $m\ell$/kg) group showed a 81.9% decrease of r$_{max}$, and 42.2% decrease of $t_{max}$, whereas the ANIT-pretreated ( $150m\ell$/kg) group showed a 53% decrease of $r_{max}$, and 2.36-fold increase of $t_{max}$, (P<0.05). These results demonstrate that the decrease of $r_{max}$ and the shortening of $t_{max}$ are characteristic features for hepatotoxicity, in contrast to the increase of $t_{max}$ and decrease of $r_{max}$ for biliary hyperplasia. Conclusion: $^{99m}$Tc-MAG3-biocytin hepatobiliary scintigraphy can distinguish hepatitis from cholestasis in mice model and may be similarly useful in humans which differentiating the cause of neonatal jaundice in clinical study.cal study.cal study.cal study.

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Comprehensive Mutation Analysis of PIK3CA, p14ARF, p16INK4a and p21Waf1/Cip1 Genes is Suggestive of a Non- Neoplastic Nature of Phenytoin Induced Gingival Overgrowth

  • Swamikannu, Bhuminathan;Kumar, Kishore S.;Jayesh, Raghavendra S.;Rajendran, Senthilnathan;Muthupalani, Rajendran Shanmugam;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2743-2746
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    • 2013
  • Background: Dilantin sodium (phenytoin) is an antiepileptic drug, which is routinely used to control generalized tonic clonic seizure and partial seizure episodes. A few case reports of oral squamous cell carcinomas arising from regions of phenytoin induced gingival overgrowth (GO), and overexpression of mitogenic factors and p53 have presented this condition as a pathology with potential to transform into malignancy. We recently investigated the genetic status of p53 and H-ras, which are known to be frequently mutated in Indian oral carcinomas in GO tissues and found them to only contain wild type sequences, which suggested a non-neoplastic nature of phenytoin induced GO. However, besides p53 and H-ras, other oncogenes and tumor suppressors such as PIK3CA, p14ARF, p16INK4a and $p21^{Waf1/Cip1}$, are frequently altered in oral squamous cell carcinoma, and hence are required to be analyzed in phenytoin induced GO tissues to be affirmative of its non-neoplastic nature. Methods: 100ng of chromosomal DNA isolated from twenty gingival overgrowth tissues were amplified with primers for exons 9 and 20 of PIK3CA, exons $1{\alpha}$, $1{\beta}$ and 2 of p16INK4a and p14ARF, and exon 2 of $p21^{Waf1/Cip1}$, in independent reactions. PCR amplicons were subsequently gel purified and eluted products were sequenced. Results: Sequencing analysis of the twenty samples of phenytoin induced gingival growth showed no mutations in the analyzed exons of PIK3CA, p14ARF, p16INK4a and $p21^{Waf1/Cip1}$. Conclusion: The present data indicate that the mutational alterations of genes, PIK3CA, p14ARF, p16INK4a and $p21^{Waf1/Cip1}$ that are frequently mutated in oral squamous cell carcinomas are rare in phenytoin induced gingival growth. Thus the findings provide further evidence that phenytoin induced gingival overgrowth as a non-neoplastic lesion, which may be considered as clinically significant given the fact that the epileptic patients are routinely administered with phenytoin for the rest of their lives to control seizure episodes.

Anti-cancer Effect of Marine Resources Against Human Colorectal Cancer Cells (해양생물 추출물의 대장암세포주에 대한 항암 작용 검색)

  • Jung, Joohee
    • Journal of Food Hygiene and Safety
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    • v.32 no.1
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    • pp.70-74
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    • 2017
  • Recently, the area of marine resources has become concerned with sources for the next generation of the bio-industry. Until present, development of the marine resources has remained limited, although a large number of these resources are considered to have potential for various significant biological activities. Most marine sponges, marine algae and coral could be used to create specific compounds for survival against a harsh environment. Therefore, it was necessary that these materials needed to be elucidated with biological activities, such as like anti-inflammatory, anti-viral or anti-cancer effects for their utilization in the bio-industry. In this study, we screened extracts of marine resources for their anti-cancer effect on human colorectal cancer cells. These resources were collected at Kosrae of Micronesia on April, 2013 and extracted with methanol. Cytotoxicity of marine resources was observed. Of a total of 20 specimens, three specimens dose-dependently demonstration inhibition of cell viability. Furthermore, cells treated with these specimens for 48h were induced p53, p21, Bax and caspase-3. The results suggest that they involved p53-mediated apoptosis. Two positive specimens (1304KO-327 and 1304KO-329) were verified as the identical materials, which are Hyrtios sp. Unfortunately 1304KO-207 was not yet classified and needed to identify in the further study. There results suggested that marine resources with positive potential in anticancer effect would be good candidates as useful bio-resources.

Occupational Aspirations of College Students in Korea : The Effect of Social Capital and Cultural Capital (대학생의 사회적 자본과 문화적 자본이 직업 포부에 미치는 효과 분석)

  • Shim, Kyoung-Sub;Seol, Dong-Hoon
    • Korea journal of population studies
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    • v.33 no.2
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    • pp.33-59
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    • 2010
  • This paper intends to find the determinants of the occupational aspirations of college students in Korea. According to Wisconsin model, the occupational aspiration of youth has a statistically significant influence on his or her actual education level and occupation choice implying that the more motivated with high-level occupational aspiration will obtain the higher level of occupation. The analysis for this study is based on the survey of undergraduate students' perception, attitude and lifestyle in Korea 2004, which was conducted against 1,947 respondents, and multiple regression model was utilized. The dependent variable for occupational aspirations was measured by the Standard International Occupational Prestige Scale (SIOPS) of Donald J. Treiman. Independent variables include social capital and cultural capital as well as demographic variables, socio-economic status, and human capital variables. Social capital variable was measured by the position generator scale of Nan Lin and Mary Dumin, and cultural capital variable was done to our original index. This study shows that social and cultural capitals are factors having significant influence on occupational aspiration, in addition to the well-known factors such as gender, human capital and the occupation of father.

Correlation Between the Parameters of Radiosensitivity in Human Cancer Cell Lines (인체 암세포주에서 방사선감수성의 지표간의 상호관계)

  • Park, Woo-Yoon;Kim, Won-Dong;Min, Kyung-Soo
    • Radiation Oncology Journal
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    • v.16 no.2
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    • pp.99-106
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    • 1998
  • Purpose : We conducted clonogenic assay using human cancer cell lines (MKN-45, PC-14, Y-79, HeLa) to investigate a correlation between the parameters of radiosensitivity. Materials and Methods : Human cancer cell lines were irradiated with single doses of 1, 2, 3, 5, 7 and 10Gy for the study of radiosensitivity and subrethal damage repair capacity was assessed with two fractions of 5Gy separated with a time interval of 0, 1, 2, 3, 4, 6 and 24 hours. Surviving fraction was assessed with clonogenic assay using $Sperman-H\"{a}rbor$ method and mathematical analysis of survival curves was done with linear-quadratic (LQ) , multitarget-single hit(MS) model and mean inactivation dose$(\v{D})$. Results : Surviving fractions at 2Gy(SF2) were variable among the cell lines, ranged from 0.174 to 0.85 The SF2 of Y-79 was lowest and that of PC-14 was highest(p<0.05, t-test). LQ model analysis showed that the values of $\alpha$ for Y-79, MKN-45, HeLa and PC-14 were 0.603, 0.356, 0.275 and 0.102 respectively, and those of $\beta$ were 0.005, 0.016, 0.025 and 0.027 respectively. Fitting to MS model showed that the values of Do for Y-79. MKN-45, HeLa and PC-14 were 1.59. 1.84. 1.88 and 2.52 respectively, and those of n were 0.97, 1.46, 1.52 and 1 69 respectively. The $\v{D}s$ calculated by Gauss-Laguerre method were 1.62, 2.37, 2,01 and 3.95 respectively So the SF2 was significantly correlated with $\alpha$, Do and $\v{D}$. Their Pearson correlation coefficiencics were -0.953 and 0,993. 0.999 respectively(p<0.05). Sublethal damage repair was saturated around 4 hours and recovery ratios (RR) at plateau phase ranged from 2 to 3.79. But RR was not correlated with SF2, ${\alpha}$, ${\beta}$, Do, $\v{D}$. Conclusion : The intrinsic radiosensitivity was very different among the tested human cell lines. Y-79 was the most sensitive and PC-l4 was the least sensitive. SF2 was well correlated with ${\alpha}$, Do, and $\v{D}$. RR was high for MKN-45 and HeLa but had nothing to do with radiosensitivity parameters. These basic parameters can be used as baseline data for various in vitro radiobiological experiments.

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Induction of Ovulation with Clomiphene Citrate (Clomiphene Citrate를 이용한 배란유도에 관한 연구)

  • Moon, S.Y.;Yoon, B.K.;Yoon, B.H.;Kim, J.G.;Lee, J.Y.;Chang, Y.S.
    • Clinical and Experimental Reproductive Medicine
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    • v.12 no.2
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    • pp.15-23
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    • 1985
  • Therapy for anovulation represents one of the more gratifying and successful type of infertility management. Despite the introduction of bromocriptine, human menopausal gonadotropin (HMG), and gonadotropin releasing hormone (GnRH), clomiphene citrate remains the mainstay of ovulation induction therapy. There is wide variability in reported rates of ovulation induction (57-91%) and conception (25-43%) following clomiphene therapy. Factors contributing to this variability among different reports are the differences in dosage and duration of therapy, different criteria utilized in selecting patients for clomiphene therapy and different luteal phase parameters of presumptive ovulation. A review of recent experience with clomiphene citrate in the Department of Obstetrics and Gynecology in Seoul National University from January, 1983 to May, 1985 yields the following conclusions: 1. Ovulation rate per total patients treated was, 69.0% 2. Pregnancy rate per total patients treated was 31.7%, and that per total patients ovulated was 45.9%. 3. Ovulation rate at the dosage level up to 150 mg/day (50.3-53.8%) was somewhat higher than that at 200 mg/day or more (33.3-34.6%), and pregnancy rate per total patients treated was comparable at each dosage level. 4. Ovulation rate per total patients ovulated at each dosage level, where ovulation and conception occurred, showed a decreasing tendency as the dosage increased, but pregnancy rate per total patients conceived was comparable except at 200 mg/day. 5. Cumulative pregnancy rate per total patients conceived in each ovulatory cycle was 68.9% in 3 cycles, 88.9% in 4 cycles, and 100% in 6 cycles.

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Physiological Responses and Subjective Sensation of Human Body Wearing OnMapsi in Heating Environment (난방환경에서 온(溫)맵시 착용에 따른 생리적 반응 및 주관적 감각)

  • Na, Young-Joo;Lee, Ji-Yun
    • Journal of the Korean Society of Clothing and Textiles
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    • v.35 no.1
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    • pp.1-12
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    • 2011
  • This study tests the performance of the recommended winter dress OnMapsi for an office worker through the analysis of skin temperature changes according to the heating environment. We tested and compared the effects of with/without undergarments for 4 male subjects in an artificial-climate chamber with two air temperatures of $19^{\circ}C$ and $22^{\circ}C$, $50{\pm}10%$ R.H. During the 60 minute experiment that simulated office work, the subjective feelings (that included thermal, humidity and comfort sensation, and skin temperature) were measured at equal intervals. The results show that the forehead and chest skin temperatures were not affected by air temperature or clothing type, while the hand and foot skin temperatures were affected at $0.3-0.9^{\circ}C$ depending on clothing type and $1.9-2.2^{\circ}C$ depending on air temperature. The mean skin temperature was decreased by the experimental time pass more with regular formal wear than with OnMapsi. The second experiment located the ambient temperature in which subjects wearing OnMapsi show equal skin temperaturesto those without undergarments at $22^{\circ}C$. Therefore it is possible to decrease heating temperatures to $18-21^{\circ}C$ in the office for winter OnMapsi wear that produces a skin temperature and thermal sensation that is the same as those at $22^{\circ}C$.

Effect of Carthami Tinctorii Fructus Herbal-acupuncture Solution(CTF-HAS) on Gene Expression in SNU484 carcinomar cells (Oligonucleotide chip을 이용한 홍화자약침액(紅花子藥鍼液)이 위암세포주(胃癌細胞柱)의 유전자(遺傳子) 발현(發顯)에 미치는 영향(影響))

  • Lee, Kyung-Min;Lim, Seong-Chul;Jung, Tae-Young;Seo, Jung-Chul;Han, Sang-Won
    • Journal of Pharmacopuncture
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    • v.8 no.1
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    • pp.31-40
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    • 2005
  • Objectives : It has long been known about the osteogenic effect of CTF-HAS on bone tissues. However, it has not been determined the effect of CTF-HAS on cancer cells. The purpose of this study is to screen the CTF-HAS mediated differentially expressed genes in cancer cells such as SNU484 gastric cancer cell lines. Oligonucleotide microarray approach were employed to screen the differential expression genes. Methods : CTF-HAS was prepared by boiling and stored at $-70^{\circ}C$ until use. Cells were treated with various concentrations of CTF-HAS(0.1, 0.5, 1.5, 10, 20mg/ml) for 24 h. Cytotoxicity was tested by MTT assay. To screen the differentially expressed genes in cancer cells, cells were treated with 1.5mg/ml of CTF-HAS. For oligonucleotide microarry assay, total RNA was used for gene expression analysis using oligonucleotide genechip (Human genome U133 Plus 2.0., Affimatrix Co.). Results : It has no cytotoxic effects on HepG2 cells in all concentration (0.1, 0.5, 1.5, 10,20mg/ml). More than twofold up-regulated genes were 5 genes. The number of more than twofold down-regulated genes was 10. Discussion : This study showed the screening of CTF-HAS mediated differentially regulated genes using combined approaches of oligonucleotide microarray. The screened genes will be used for the better understanding in therapeutic effect of CTF-HAS on cancer field.

Biotransformation of Ginsenoside Rb1, Crocin, Amygdalin, Geniposide, Puerarin, Ginsenoside Re, Hesperidin, Poncirin, Glycyrrhizin, and Baicalin by Human Fecal Microflora and Its Relation to Cytotoxicity Against Tumor Cells

  • Kim, Young-Suk;Kim, Jung-Jin;Cho, Ki-Ho;Jung, Woo-Sang;Moon, Sang-Kwan;Park, Eun-Kyung;Kim, Dong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.18 no.6
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    • pp.1109-1114
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    • 2008
  • To understand the role of intestinal microflora in the biological effect of functional herbs, which have been used in Korea, Japan, and China as traditional medicines, and suggest new bioactive compounds transformed from herbal constituents, the metabolic activities of the functional herb components (ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, poncirin, hesperidin, glycyrrhizin, and baicalin) toward their bioactive compounds (compound K, crocetin, benzaldehyde, genipin, daidzein, ginsenoside Rh1, ponciretin, hesperetin, 18b-glycyrrhetic acid, and baicalein) were measured in fecal specimens. The metabolic activities of these components were $882.7{\pm}814.5$, $3,938.1{\pm}2,700.8$, $2,375.5{\pm}913.7$, $1,179.4{\pm}795.7$, $24.6{\pm}10.5$, $11.4{\pm}10.8$, $578.8{\pm}206.1$, $1,150.0{\pm}266.1$, $47.3{\pm}58.6$, and $12,253.0{\pm}6,527.6\;{\mu}mol/h/g$, respectively. No differences were found in the metabolic activities of the tested components between males and females, although these metabolic activities between individuals are extensively different. The metabolites of functional herb components showed more potent cytotoxicity against tumor cells than nonmetabolites. These findings suggest that intestinal microflora may activate the pharmacological effect of herbal food and medicines and must be the biocatalytic converter for the transformation of herbal components to bioactive compounds.

Endometrial Ultrasonography as a Predictor of Pregnancy in an In Vitro Fertilization Program (체외수정시술의 결과 예측지표로서의 자궁내막초음파술)

  • Shin, Chang-Jae;Kim, Sung-Soo
    • Clinical and Experimental Reproductive Medicine
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    • v.21 no.1
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    • pp.13-20
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    • 1994
  • Status of endometrium is a very important factor which influences the implantation of fertilized embryos. In this study, we evaluated the possibility that the endometrial depth and pattern assessed by vaginal sonography on the day of human chorionic gonadotropin (HCG) injection in in vitro fertilization (IVF) cycles could be used to predict the IVF outcome. A total of 112 cycles using gonadotropin releasing hormone agonist (GnRHa) for ovulation induction were evaluated. We classified all patients into group A(<9mm) or group B(${\geq}$ 9mm) according to endometrial depth, and into group l(hyperechogenic), group 2(isoechogenic) or group 3(hypoechogenic and triple line) according to endometrial pattern. The other classification was made considering both endometrial depth and pattern. There was no significant correlation between serum estradiol level and endometrial sonographic findings(depth and pattern)(p>0.05). The pregnancy rate of group A(31.3%) did not differ significantly from that of group B(43.7%), but no pregnancies were found in any patients with endometrial depth less than 6mm. The pregnancy rate was 40%, 35.7%, and 44.6 % for group 1, gorup 2, and group 3, respectively, but there was no statistically significant difference between these groups(p>0.05). In combined classification, there was a trend of higher pregnancy rate in case of endometrial depth greater than 9mm and hypoechogenic triple line pattern, but there was no statistically significant differences between these groups(p>0.05). The conclusion from the present data is that endometrial ultrasonography on the day of hCG administration had no predictive value for conception in IVF cycles.

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