• Title/Summary/Keyword: Human liver

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Study of Mutual Understanding and Human Body (몸과 소통에 관한 연구)

  • Chough, Won-Joon;Kim, Yeong-Mok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.4
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    • pp.822-834
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    • 2007
  • This study searched the philosophical and medical thought of mutual understanding and human body. Mutual understanding is a fundamental problem in all branches of oriental studies. In other words, mutual understanding becomes the existential foundation of heaven-earth-human(三才). So human beings, heaven and the earth can't exist if there is no mutual understanding. It comes out the problem of self-consciousness in philosophy, and qi movement pattern like upward, downward, inward and outward movement in traditional korean medicine. Human beings have mutual understandings with heaven and the earth from a macroscopic standpoint, on the other side the human body from a microscopic standpoint. Qi movement is the mutual understanding and response of qi in human body, so with which the physiological functions and pathologic changes of viscera and bowels comes out. Therefore we want to present how to complete qi movement between viscera-bowels and organs to examine mutual understandings in human body closely. The results was summarized as follows; First, upbearing the clear yang and down bearing the turbid yin of spleen-stomach is main pivot of upward and downward of qi movement, and it is true form of mutual understandings between viscera and bowels, so upward, downward, inward and outward movement of whole viscera and bowels can be controlled by spleen-stomach. Second, by restraining relationships between downward heart fire and upward kidney water, heart fire and kidney water have close communications physiologically and pathologically as upper-lower, yin-yang and water-fire. Third, by restraining relationships between upbearing and effusion of liver and purification and down-sending of lung, liver and lung are outer circles of upward and downward movement, so they have antagonistic functions. Firth, by the relationships between upbearing the clear and down bearing the turbid of spleen-stomach and free coursing of liver, free coursing of liver-gallbladder is the essential requirement that it certify transportation and transformation of spleen-earth, so the disease of liver-gallbladder induce spleen-stomach disease pattern to affect its function of transportation and transformation. Fifth, by spleen and kidney, spleen yang is based on kidney yang, so the weakness of kidney yang can affect the function of transportation and transformation of spleen-stomach as it can't warm spleen earth. Sixth, by homogeny of liver-kidney, essence and blood of liver-kidney and ministerial fire of liver-kidney have mutal generation and limitation physiologically and they mutually are affected in pathologically.

Metabolism of YH1885 by Rat, Dog, Monkey and Human Liver S9 Fractions

  • Kim, Eun-Joo;Roh, Jung-Koo;Green, Carol
    • Biomolecules & Therapeutics
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    • v.6 no.3
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    • pp.283-288
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    • 1998
  • YH 1885 (5,6-dimethyl -2-(4-fluorophenylamino)-4-(1-methyl -1,2,3,4-tetrahydroisoquinolin -2- yl) pyrimidine hydrochloride) was developed as an antiulcer drug. The objective of this study was to examine a comparative metabolism of YH1885 in rat, dog, monkey and human liver tissues and to determine the metabolite profiles produced by the four species. YH1885 was metabolized by liver 59 fractions from all four species. Control incubations containing 59 fraction but no cofactors, contained essentially no metabolites. Metabolism of YH1885 apparently became saturated in the concentration range studied because the % of YH 1885 metabolized decreased with increasing drug concentration for all four species. Six to nine metabolite peaks were detected in the incubations and the particular profile of metabolites varied with species. The total amount of metabolites formed by liver microsomes from human and monkey were less than microsomes from rat or dog. The major metabolite peak formed by rat liver 597actions fluted near the solvent front on the HPLC or remained at the origin in TLC, indicating that it contained one or more polar metabolites. Dog liver 59 fractions incubations contained four major metabolites that each accounted for about 15 to 20 % of the total radioactivity at the low concentration of YH1885. The metabolite profiles of YH1885 appeared to be similar in incubations with rhesus monkey and human liver 59 fraction. The amount of metabolites formed by rhesus monkey liver preparations was greater than that of human liver that contained prominent metabolite peaks with approximate relative retention time of 0.14 and 0.43.

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Isolation and Characterization of cDNA Encoding Pyridoxal Kinase from Ovine Liver

  • Lee, Hyun-Shik;Choi, Soo-Young;Kwon, Oh-Shin
    • BMB Reports
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    • v.32 no.5
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    • pp.502-505
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    • 1999
  • cDNA fragments of ovine liver pyridoxal kinase were amplified by PCR using degenerate oligonucleotide primers derived from partial amino acids sequences of the enzyme. Using PCR products as probes, several overlapping cDNA clones were isolated independently from an ovine liver and a human brain cDNA library. The largest cDNA clone for each was selected for sequence analysis. The ovine liver cDNA encodes a polypeptide of 297 amino acid residues with Mr of 32,925, whereas the human clone is comprised of an open reading frame encoding 312 amino acid residues with Mr of 35,102. The deduced sequence of the human brain enzyme is completely identical to that of human testes cDNA recently reported (Hanna et al., 1997). The ovine enzymes have approximately 77% sequence identity with the human enzyme although the two sequences are completely different in the N-terminus comprising 32 residues. This result suggests that pyridoxal kinase is highly homologous in mammalian species.

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Estimation of Attenuation Coefficient based on Ultrasonic Image for quantification of the Liver Diseases (간 병변의 정량화를 위한 초음파 영상 신호의 감쇄상수 추정)

  • 우광방;신동호;이성모;신영민;이노성;오성권
    • Journal of the Korean Institute of Telematics and Electronics
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    • v.25 no.1
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    • pp.49-55
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    • 1988
  • To provide a quantitative parameter of evaluating diagnosis of the liver diseases accurately, the ultrasonic attenuation coefficient was estimated from liver phantoms, 15 normal human livers and 30 liver disease patients. Two kind of phantoms(No.1: 1552m/s, No.2: 1562m/s) which have velocity (1560m/s) similar to that in human liver were constructed and their ultrasonic attenuation coefficients were determined. In this paper the spectral-shift approach and spectral-difference approach were used for estimating ultrasonic attenuation coefficient, \ulcornerdB/Cm.MHz). These two approaches were utilized to esitmate for 15 normal humans without any liver disease and 30 liver disease patients. The results indicate that the two types of phantoms produce the value of near the suggested value of 0.5 and the attenuation coefficients of hepatoma, normal liver, corrhosis, fatty liver and hepatitis show decreasing value in order named, suggesting that the present study can be of clinical value incorrelating the estimated attenuation coefficidents with the liver diseases.

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Quality and Availability Evaluation of Human Hepatocytes Isolated from Resected Partial Livers for Toxicology and Drug Metabolism Studies in Korea (독성 및 약물대사 연구를 위한 한국인 부분 간 유래 간세포의 품질 및 활용성 평가)

  • Noh, Jeong-Kwon;Jang, In Keun;Kim, Hyo Eun;Lee, Jong Eun;Yang, Mal Sook;Jang, Eun Mi;Lee, Ji-Hyun;Park, Hey-Jung;Kim, Young-A;Lee, Suk-Koo;Jeong, Ho-Sang;Ahn, Joon-Ik;Lee, Doo-Hoon
    • KSBB Journal
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    • v.29 no.1
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    • pp.58-66
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    • 2014
  • Demand for in vitro pharmacological evaluation and toxicity test using human hepatocytes has been increasing. In USA and Europe, human hepatocytes obtained from donated whole liver unsuitable for transplantation were distributed to researchers and deposited in cell bank facility as cryopreserved vial. In Korea, however, incidence of transplantation- inappropriate whole liver has been quite low and the whole livers almost have so severe liver disease such as fatty or fibrotic liver that cannot meet the demand. In this study we aimed to isolate human hepatocytes from liver resection surgery-originated partial liver, and assure the isolated human hepatocytes and its cryopreserved hepatocytes to be qualified for the in vitro pharmacological evaluation and drug toxicity tests. We compared those with commercially available human hepatocyte, BD $GenTest^{TM}$ by cell morphology, hepatic gene expression, urea synthesis, albumin secretion, ammonia removal, and cytochrome P450 induction activities. Changes in hepatotoxic gene expression after cryopreservation are evaluated with a typical hepatotoxic drug, acetaminophen. Consequently, the fresh hepatocytes from the partial liver and its cryopreserved hepatocytes expressed their intrinsic hepatic functions well and showed equal hepatotoxicity gene expression trend regardless to cryopreservation. Therefore, liver resection surgery-originated partial liver can be used as a useful source of human hepatocytes for various pharmacological and hepatotoxicity test.

Cloning and Expression of Human Liver UDP-Glucuronosyltransferase cDNA, UDPGTh2

  • Dong, Misook;Owens, Ida-S.;Sheen, Yhun-Yhong
    • Archives of Pharmacal Research
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    • v.20 no.5
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    • pp.459-464
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    • 1997
  • The human liver cDNA clone UDPGTh2, encoding a liver UDP-glucuronosyltransferase (UDPGT) was isolated from a .gamma. gt 11 cDNA library by hybridization to mouse transferase cDNA clone, UDPGTm1. UDPGTh2 encoded a 529 amino acid protein with an amino terminus membrane-insertion signal peptide and a carboxyl terminus membrane-spanning region. There were three potential asparagine-linked glycosylation sites at residues 67, 68, and 315. In order to obtain UDPGTh2 protein encoded from cloned human liver UDP-glucuronosyltransferase cDNA, the clone was inserted into the pSVL vector (pUDPGTh2) and expressed in COS 1 cells. The presence of a transferase with Mr-52,000 in transfected cells cultured in the presence of $[^{35}S]$ methionine was shown by immunocomplexed products with goat antimouse transferase IgG and protein A-Sepharose and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The expressed UDPGT was a glycoprotein as indicated by electrophoretic mobility shift in Mr-3,000-4,000 when expressed in the presence of tunicamycin. The extent of glycosylation was difficult to assess, although one could assume that glycosyl structures incorporated at the level of endoplasmic reticulum were always the core oligosaccharides. Thus, it is likely that at least two moieties inserted can account for the shift of Mr-3,000-4,000. This study demonstrates the cDNA and deduced amino acid sequence of human liver UDP-glucuronosyltransferase cDNA, UDPGTh2.

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In Vitro Metabolism of a New Neuroprotective Agent, KR-31543 in the Human Liver Microsomes : Identification of Human Cytochrome P450

  • Ji, Hye-Young;Lee, Seung-Seok;Yoo, Sung-Eun;Kim, Hosoon;Lee, Dong-Ha;Lim, Hong;Lee, Hye-Suk
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.239-245
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    • 2004
  • KR-31543, (2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2 -methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran, is a new neuroprotective agent for preventing ischemia-reperfusion damage. This study was performed to identify the metabolic pathway of KR-31543 in human liver microsomes and to characterize cytochrome P450 (CYP) enzymes that are involved in the metabolism of KR-31543. Human liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of two metabolites, M1 and M2. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC/MS/MS analysis with a synthesized authentic standard, and M2 was suggested to be hydroxy-KR-31543. Correlation analysis between the known CYP enzyme activities and the rates of the formation of M 1 and M2 in the 12 human liver microsomes have showed significant correlations with testosterone 6$\beta$-hydroxylase activity (a marker of CYP3A4). Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. These results provide evidence that CYP3A4 is the major isozyme responsible for the metabolism of KR-31543 to M1 and M2.

Revisiting Hepatoprotective Natural Products from a Biological Point of View

  • Kim, Hong-Pyo;Kim, Young-Choong
    • Natural Product Sciences
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    • v.17 no.3
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    • pp.165-174
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    • 2011
  • Naturally occurring small molecules from plants, microorganisms, and animals allow the design of drugs that can be beneficial in virtually all kinds of human diseases. Liver diseases with diverse etiologies such as viral infection, chemical intoxication, and metabolic fat accumulation are one of the leading causes of human mortality. Unfortunately, however, there are few effective drugs available capable of stopping or reversing the progress of liver disease. Here, we discuss the current advances in developing hepatoprotective natural products for several arrays of liver disease pathogenesis.

Structural and Quantitative Expression Analyses of HERV Gene Family in Human Tissues

  • Ahn, Kung;Kim, Heui-Soo
    • Molecules and Cells
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    • v.28 no.2
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    • pp.99-103
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    • 2009
  • Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of several human diseases as multi-copy members in the human genome. Their gene expression profiling could provide us with important insights into the pathogenic relationship between HERVs and cancer. In this study, we have evaluated the genomic structure and quantitatively determined the expression patterns in the env gene of a variety of HERV family members located on six specific loci by the RetroTector 10 program, as well as real-time RT-PCR amplification. The env gene transcripts evidenced significant differences in the human tumor/normal adjacent tissues (colon, liver, uterus, lung and testis). As compared to the adjacent normal tissues, high levels of expression were noted in testis tumor tissues for HERV-K, in liver and lung tumor tissues for HERV-R, in liver, lung, and testis tumor tissues for HERV-H, and in colon and liver tumor tissues for HERV-P. These data warrant further studies with larger groups of patients to develop biomarkers for specific human cancers.

Analysis of Partial cDNA Sequence from Human Fetal Liver

  • Kim, Jae-Wha;Song, Jae-Chan;Lee, In-Ae;Lee, Young-Hee;Nam, Myoung-Soo;Hahn, Yoon-Soo;Chung, Jae-Hoon;Choe, In-Seong
    • BMB Reports
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    • v.28 no.5
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    • pp.402-407
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    • 1995
  • Single-run Partial cDNA sequencing was conducted on 1,592 randomly selected human fetal liver cDNA clones of Korean origin to isolate novel genes related to liver functions. Each partial cDNA sequence determined was analyzed by comparing it with the databases. GenBank, Protein Information Resource (PIR) and SWISS-PROT Protein Sequence Data Bank. From a set of 1.592 cDNA clones reported here, 1,433 (90.0% of the total) were informative cDNA sequences. The other 159 clones were identified as DNA sequences which had originated from the cloning vector. Among 1,433 informative partial cDNA sequences, 851 (59.3%) clones were revealed to be identical to known human genes. These known genes have been classified into 225 different kinds of genes. In addition, 340 clones (23.7%) showed various degrees of homology to previously known human genes. Ninety four (6.6%) clones contained various repeated sequences. Twenty four (1.7%) partial cDNA sequences were found to have considerable homology to known genes from evolutionarily distant organism such as yeast, rice, Arabidopsis, mouse and rat, based on database matches, whereas 124 (8.7%) had no Significant matches. Human homologues to functionally characterized genes from different organisms could be classified as candidates for novel human genes of similar functions. Information from the partial cDNA sequences in this study may facilitate the analysis of genes expressed in human fetal liver.

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