Distinct clinical courses according to presenting phenotypes and their correlations to <i>ATP7B</i> mutations in a large Wilson's disease cohort

Lee, Beom H.,Kim, Joo H.,Lee, Sun Y.,Jin, Hye Y.,Kim, Kwi‐,Joo,Lee, Jin‐,Joo,Park, Jung‐,Young,Kim, Gu‐,Hwan,Choi, Jin‐,Ho,Kim, Kyung M.,Yoo, Han‐,Wook Blackwell Publishing Ltd 2011 Liver International Vol.31 No.6

<P><B>Abstract</B></P><P><B>Introduction and aims: </B> Wide phenotypic and genotypic heterogeneities in Wilson's disease (WD) have been reported, hampering the study of their correlations. The goal of this study was to identify the factors related to these diversities.</P><P><B>Methods: </B> Clinical courses and molecular genetic characteristics were analysed in 237 unrelated Korean WD families. The average follow‐up period was 8.2 ± 5.8 years.</P><P><B>Results: </B> Presenting phenotypes were classified as H1 (12.2%), H2 (42.4%), N1 (21.6%), N2 (0.4%), NX (0.4%), presymptomatic (22.4%) and other (0.4%), modifying the guidelines by Ferenci and colleagues. Age at presentation was youngest and cirrhosis was rarest in the presymptomatic group. Decompensated cirrhosis was the highest in the H1 group. Favourable outcome was rarest in the N1 group. Forty‐seven (11 novel) <I>ATP7B</I> mutations were identified in 85% of the 474 alleles. Multiplex ligation‐dependent probe amplification assays in <I>ATP7B</I> and analyses of <I>ATOX1</I> and <I>COMMD1</I> genes identified no additional mutations. Yeast complementation assays demonstrated functional perturbation of the seven novel missense mutants. Five major mutations, p.Arg778Leu, p.Ala874Val, p.Asn1270Ser, p.Lys838SerfsX35 and p.Leu1083Phe, accounted for 63% of the alleles. H1 was more common, age at presentation was younger and N1+N2+NX tended to be less common in patients with nonsense, frame shifting or splicing mutations than in those with missense mutations alone. Patients with both mutations in the transduction (Td) or the ATP hinge domain showed presymptomatic or hepatic manifestations but no neurological manifestation.</P><P><B>Conclusions: </B> The presenting phenotype strongly affects the clinical outcome of WD, and is related to the <I>ATP7B</I> mutation type and location, providing an evidence for genotype–phenotype correlations in WD.</P>

Hospital-based Influenza Morbidity and Mortality (HIMM) Surveillance for A/H7N9 Influenza Virus Infection in Returning Travelers

Song, Joon Young,Noh, Ji Yun,Lee, Jacob,Woo, Heung Jeong,Lee, Jin Soo,Wie, Seong-Heon,Kim, Young Keun,Jeong, Hye Won,Kim, Shin Woo,Lee, Sun Hee,Park, Kyung-Hwa,Kang, Seong Hui,Kee, Sae Yoon,Kim, Tae H KOREAN ACADEMY OF MEDICAL SCIENCE 2018 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.33 No.7

<P>Since 2013, the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system began a H7N9 influenza surveillance scheme for returning travelers in addition to pre-existing emergency room (ER)-based influenza-like illness (ILI) surveillance and severe acute respiratory infection (SARI) surveillance. Although limited to eastern China, avian A/H7N9 influenza virus is considered to have the highest pandemic potential among currently circulating influenza viruses. During the study period between October 1st, 2013 and April 30th, 2016, 11 cases presented with ILI within seven days of travel return. These patients visited China, Hong Kong, or neighboring Southeast Asian countries, but none of them visited a livestock market. Seasonal influenza virus (54.5%, 6 among 11) was the most common cause of ILI among returning travelers, and avian A/H7N9 influenza virus was not detected during the study period.</P>

Hepatic Cirrhosis Occurring in a Young Woodchuck(Marmota monax) Due to Vertical Transmission of Woodchuck Hepatitis Virus(WHV)

Kyu-shik Jeong,정원일,Jae-yong Chung,Mi-young An,Chae-yong Jung,Gyoung-jae Lee,Jong-soo Kang,Byeong-cheol Kang,Young-heun Jee,Bruce H Williams,Young-oh Kwon,Da-hee Jeong 대한수의학회 2003 Journal of Veterinary Science Vol.4 No.2

Cirrhosis Occurring in a Young Woodchuck (Marmota monax) Due to Vertical Transmission of Woodchuck Hepatitis Virus (WHV)Da-hee Jeong, Won-il Jeong, Jae-yong Chung, Mi-young An, Chae-yong Jung, Gyoung-jae Lee1, Jong-soo Kang1, Byeong-cheol Kang2, Young-heun Jee3, Bruce H Williams4, Young-oh Kwon5 and Kyu-shik Jeong*College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea1Shinwon Scientific Co., LTD, Research Institute, Suwon, Korea2Clinical Research Institute, Seoul National University, Seoul 110-744, Korea3College of Veterinary Medicine, Jeju National University, Jeju 690-756, Korea

Time-dependent effects of Klebsiella pneumoniae endotoxin on the pharmacokinetics of chlorzoxazone and its main metabolite, 6-hydroxychlorzoxazone, in rats: restoration of the parameters in 96 hour in KPLPS rats to control levels

Jung, Hye Y.,Kang, Hee E.,Choi, Young H.,Kim, So H.,Lee, Myung G. John Wiley Sons, Ltd. 2009 BIOPHARMACEUTICS AND DRUG DISPOSITION Vol.30 No.8

<P>It has been reported that chlorzoxazone (CZX) was primarily metabolized via hepatic Cyp2e1 to form 6-hydroxychlorzoxazone (OH-CZX) in rats, and the activity of aniline hydroxylase (a Cyp2e1 marker) in the liver was significantly decreased in rats at 24 h after pretreatment with lipopolysaccharide derived from Klebsiella pneumoniae (24 h KPLPS rats), whereas the levels were not changed at 2 h and 96 h in the KPLPS rats. Thus, the time-dependent pharmacokinetic parameters of CZX and OH-CZX were evaluated after the intravenous administration of CZX (20 mg/kg) to control rats, and the 2 h, 24 h and 96 h KPLPS rats along with the time-dependent changes in the protein expression of hepatic Cyp2e1. After the intravenous administration of CZX to 24 h KPLPS rats, the AUC<SUB>0–2 h</SUB> of OH-CZX and AUC<SUB>OH-CZX, 0–2 h</SUB>/AUC<SUB>CZX</SUB> were significantly smaller (by 40.5% and 71.2%, respectively) than those of controls due to the significant decrease (by 75.3%) in the protein expression of hepatic Cyp2e1. However, in 96 h KPLPS rats, the pharmacokinetic parameters of both CZX and OH-CZX were unchanged compared with controls due to the restoration of the protein expression of hepatic Cyp2e1 to control levels. These observations highlighted the existence of the time-dependent effects of KPLPS on the pharmacokinetics of CZX and OH-CZX in rats. Copyright © 2009 John Wiley & Sons, Ltd.</P>

Comparative Studies of Atmospheric Pressure Plasma Characteristics Between He and Ar Working Gases for Sterilization

Young Sik Seo,Mohamed, Abdel-Aleam H,Kyung Chul Woo,Hyun Wook Lee,Jae Koo Lee,Kyong Tai Kim IEEE 2010 IEEE transactions on plasma science Vol.38 No.10

<P>Helium (He) and Argon (Ar) atmospheric pressure plasma jets operated with low-frequency power source are designed and studied. The current and voltage waveforms, formation of plasma jets, estimated rotational and vibrational temperatures, optical emission spectra, and numerical simulations for He and Ar gases are investigated to analyze the plasma characteristics. Ar plasma shows higher discharge current and many instantaneous current peaks compared with He plasma. For gas flow between 1 and 7 L/min and applied voltage between 3 and 10 kV, no significant changes in Ar plasma are observed. He plasma is found to be sensitive as far as gas flow rate and applied voltage are concerned. This sensitivity is associated with a transition from laminar to turbulent mode of gas flow. The estimated gas temperatures show higher values for Ar plasma than those of He plasma. Ar plasma jet emits extremely high intensity of OH (305 nm ~312 nm) and O (777 nm) compared with that emitted from He plasma jet. High concentration of OH and O in Ar plasma is related with high density of electrons with 4-5 eV, which is in the range of the dissociation energy of H-H, O-H, and O=O bonds. As a result, wider sterilization area and higher sterilization efficacy in indirect treatment are observed for Ar plasma than He plasma.</P>

피부감작성에 있어 Local lymph node의 반응성 연구

이종권,박재현,김형수,정승태,엄준호,황인창,장은정,윤소미,남기택,허용,오혜영 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

알레르기설 접촉 괴부염은 다양한 화학물질에 의해 유포될 수 있다. 화학물질이 피부 감작성을 알 킬 수 있는지 여부는 전통적으로 기니픽을 사용한 등물모겔이 이용되어 쏜으나, 최근에는 마우스를 이용한 local Iymph node assily tLLNA) 발법 개발이 요구되고 있떠 본 연구는 focal Iymph not assa)·의 시험방법을 개발하고, 감작을 일으키는 기전을 파악하고자 하였다. 콕헝물질로는 패표적 접촉 알러전인 DffCB(2,4-dinitrochlorobenzone), 호홉 알러젠인 fDl(toluene diisocyanate), 약한 알러젠인Cf.(o-kerplcinamaldehl,do:4, 강한 자극물질인 SLS(sodum lauryl sulfate)를 사용하였다. 각 시험물질 2sr4를 적절한 농도로 6-8주령의 암컷 Balb/c 마우스의 귀의 배측에 3일간 도포한 후 5일째에 부검하여 이개림프절, 귀의 변화 등을 관찰하였다. DNCB, TDI를 도포한 마우스의 이개 림프절의 중량은 대조군에 비해 증가하였으며, 고농도의 HCA를 투여한 마우스에서의 림프절 중량도 증가하였다. SLS를 투여한 군의 림프걸치 중량은 저농도에서는 변화가 없었으나, 고농도에서는 중량이 증가하였다. 꼬리정맥에 3H-thymidine을 투여하여 림프절의 증식정도를 파악한 결과, BNCB를 도포한 군에서는 프절의 증식지수(Stimulation 1.Idex, Sl)가 용량별로 20.3, 24.6, 27.5로 관찰되었으며, TDI군에서는 각 19.0, 29.T, 42.3으로 관찰되첬고 HCA군에서는 각각 3.8, 9.7, 19.8로 관찰되었다. sLs군에서는 0.8 3.7, 6.6으로 관찰되었다. 이잖끈 결과 fH-thynudine을 이용한 피부 감작성 평가는 기니픽을 대체할수 있는 방법으로 _평가되었다. 그러나 방사선이용이라는 단점과 강한 자극성물질에서의 위양성 반응이 관찰되어 BrdU(Eromodeoklpuddine) 면역조직차학기법으로 시험한 결과 비방사선법도 이용 가능함을 알 수 있었다. 또는 TDI를 처리한 마우스의 림프절에서 cytoklne의 발현을 RT-PCR로 측정한 결과 IL-2 IL-4, U-10과 INf-r의 mRNA발현이 증가하였으며, HCA를 처리한 경우에는 토-4, IL-10. INf-γ mRNA의 발현이 증가 하였다. 또한 B리CB의 경우에는 U-4의 발현이 증가하였다. 그러나, sLs의 경우에는 IL-?, IL-4, 0--10 과 rNF-r꼭 발현이 증가되지 않았다. 이러한 결과는 LLNA를 이용한 c번okine의 n)교NA발현이 유용싼 측정 지포중 하나가 될 수 있을 것으로 생각되며. 특히 IL-4의 발현정도의 증가는 알레르기 유발성을 평가할 유용한 생체지표의 하나가 될 수 있을 것으로 생각되어진다. Allergic contact dermatitis (skin sensitization) may be caused by a wide variety of chemicals. A murine local lymph node assay(LLNA) has been developed as an alternative to guinea pig models for assessing the contact sensitization potential of chemical. First, the objective of this study was to evaluate allergenecity of chemicals by LLNA. Secondly, we aimed to investigate the possibility of development of non-radio isotopic endpoint for LLNA using immunohistochemistry. Thirdly, we aimed to analyze cytokine mRNA expression of draining lymph node cell in mice exposed to chemical allergen and irritant. In this study, contact allergen, dinitrochlorobenzone (DNCB), respiratory allergen toluene diisocyanate (TDI) and moderate allergen, α-hexylcinnamaldehyde (HCA) were used as positive chemicals and the irritant, sodium lauryl sulfate(SLS) also used as reference chemical. The stimulation index (SI) of lymph node cell in the mice treated with allergens. DNCB, TDI, and HCA were more increased dose-dependently compared to vehicle control by ^(3)H-thymidine uptake. And SI of lymph node cell in strong irritant, SLS were also increased dose-dependently compared to control. The BrdU(Bromodeoxyuridine) LI of lymph node in DNCB and TDI were dramatically increased campared to that of control. However, the LI of lymph node in SLS were not significantly increased compared to vehicle control. This data represents that BrdU LI of lymph node could be one of useful method for screening for irritant and allergen. The expression of IL-2, IL-4, IL-10 and IFN-γ mRNA was increased in draining auricular lymph node cell of the mice treated with TDI by RT-PCR. The level of IL-4, IL-10 and IFN-γmRNA was increased in mice treated with HCA. The expression of IL-4 was increased in lymph node cell of mice treated with DNCB. However, the level of IL-2, IL-4, IL-10 and IFN-γ in lymph node cell of mice treated with SLS was not increased. These results suggest the measurement for increase in level of IL-4 mRNA expression could by one of the method for screening the allergenic potential.

정상 성인 요통 및 요추간판탈출증 환자에서의 H-Reflex에 대한 고찰 : In Normal Dault, Lambago and Lumbar Disc Patients

이화룡,김헌주,이상철,이규호,김달수 대한신경외과학회 1980 Journal of Korean neurosurgical society Vol.9 No.1

Since the early discovery of H-reflex by Hoffmann in 1918 there have been a great number of articles in the literature suggesting its clinical uses by Magladery in the early 1950. Our experiments about about measurement of latent time in H-reflex were performed on 40 normal male adult (composed of medicos and medical officers) and 82 patients (lumbago40, lumbar disc 42) admitted at CAPGH from January '79. to August '79. The result about normal adult are as follows: 1) The mean value and the standard deviation of the latent time in normal adult (height 171±5.14cm) is 27.74 ± 1.86 maec at rihht leg, 27.77±1.64 msec at left one respectively. 2) There may be a linear relationship between latency and the height of normal adult and the difference between right and left is revealed 0.15±0.19 msec. We compare the measurement on the 82 patients group with the normal adult experimental groups in addition literatures review.

Molecular identification and functional delineation of a glutathione reductase homolog from disk abalone (<i>Haliotis discus discus</i>): Insights as a potent player in host antioxidant defense

Herath, H.M.L.P.B.,Wickramasinghe, P.D.S.U.,Bathige, S.D.N.K.,Jayasooriya, R.G.P.T.,Kim, Gi-Young,Park, Myoung Ae,Kim, Chul,Lee, Jehee Elsevier 2017 FISH AND SHELLFISH IMMUNOLOGY Vol.60 No.-

<P><B>Abstract</B></P> <P>Glutathione reductase (GSR) is an enzyme that catalyzes the biochemical conversion of oxidized glutathione (GSSG) into the reduced form (GSH). Since the ratio between the two forms of glutathione (GSH/GSSG) is important for the optimal function of GSH to act as an antioxidant against H<SUB>2</SUB>O<SUB>2</SUB>, the contribution of GSR as an enzymatic regulatory agent to maintain the proper ratio is essential. Abalones are marine mollusks that frequently encounter environmental factors that can trigger the overproduction of reactive oxygen species (ROS) such as H<SUB>2</SUB>O<SUB>2</SUB>. Therefore, we conducted the current study to reveal the molecular and functional properties of a GSR homolog in the disk abalone, <I>Haliotis discus discus</I>. The identified cDNA sequence (2325 bp) has a 1356 bp long open reading frame (ORF), coding for a 909 bp long amino acid sequence, which harbors a pyridine nucleotide-disulfide oxidoreductase domain (171–246 aa), a pyridine nucleotide-disulfide oxidoreductase dimerization domain, and a NAD(P)(+)-binding Rossmann fold superfamily signature domain. Four functional residues: the FAD binding site, glutathione binding site, NADPH binding motif, and assembly domain were identified to be conserved among the other species. The recombinant abalone GSR (rAbGSR) exhibited detectable activity in a standard glutathione reductase activity assay. The optimum pH and optimal temperature for the reaction were found to be 7.0 and 50 °C, respectively, while the ionic strength of the medium had no effect. The enzymatic reaction was vastly inhibited by Cu<SUP>+2</SUP> and Cd<SUP>+2</SUP> ions. A considerable effect of cellular protection was detected with a disk diffusion assay conducted with rAbGSR. Moreover, an MTT assay and flow cytometry confirmed the significance of the protective role of rAbGSR in cell function. Furthermore, <I>AbGSR</I> was found to be ubiquitously distributed in different types of abalone tissues. <I>AbGSR</I> mRNA expression was significantly upregulated in response to three immune challenges: <I>Vibrio parahaemolyticus</I>, <I>Listeria monocytogenes</I>, and lipopolysaccharide (LPS), thus indicating its possible involvement in host defense mechanisms during pathogenic infections. Taken together, the results of the current study suggest that AbGSR plays an important role in antioxidant-mediated host defense mechanisms and also provide insights into the immunological contribution of AbGSR.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We identified a glutathione reductase homolog (AbGSR) from disk abalone. </LI> <LI> AbGSR resembled functionally important domain architecture of GSR family. </LI> <LI> Recombinant AbGSR confirmed its biochemical properties via enzymatic assays. </LI> <LI> First functional antioxidant properties assessment of a molluscan GSR. </LI> <LI> <I>AbGSR</I> expression was modulated upon induced pathogen stress in gill and hemocytes. </LI> </UL> </P>

비혈연간 동종골수이식에 의해 치료된 중증 재생불량성빈혈 1예

김현중,이홍기,이방훈,이창근,이종태,정현식,김원석,윤성수,강원기,박근칠,김대식,고영혜,박찬형 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1

비혈연간 동종골수이식은 혈연간 동종골수이식이 불가능한 환자에서 기존의 면역역제요법으로 효과가 없었던 경우나 재발한 경우에 적응증이 될수 있다. 이식 거부와 이식편대숙주병의 발생이 골수 이식의 성공률을 감소시키므로, 보다 강력한 conditioning regimen의 사용과 T cell이 제거된 골수를 사용하는 것이 필요하다. 기존의 high dose corticosteroid나 cyclosporine에 대하여 불응성인 이식편대숙주병의 치료를 위해서 ATG와 Mycophenolate mofetil (Cellcept®) 의 사용이나 Tacrolimus, Methotrexate와 같은 다른 면역억제제치료를 고려해 볼 수 있다. It is known that allogenic bone marrow transplantation is the most effective treatment for aplastic anemia. However, this treatment is only applicable to a minority of patients because the proportion of patients who have HLA-matched siblings about 25% to 30% of all the aplastic anemia patients. In the case of the absence of HLA-matched donor, unrelated allogenic bone marrow transplantation is considered. However, (because of severe acute and chronic GVHD and graft failure) the success rate of this approach is only 20~30%. Recently, it was reported that increased immunosuppressive condition combined with T cell depletion of the marrow graft would result in greater success. There was no case of successfully treated aplastic anemia patient by unrelated allogenic bone marrow transplantation in Korea. Here, we report a case of severe aplastic anemia successfully treated with unrelated allogenic bone marrow transplantation.

Novel amine-functionalized iron trimesates with enhanced peroxidase-like activity and their applications for the fluorescent assay of choline and acetylcholine

Valekar, Anil H.,Batule, Bhagwan S.,Kim, Moon Il,Cho, Kyung-Ho,Hong, Do-Young,Lee, U-Hwang,Chang, Jong-San,Park, Hyun Gyu,Hwang, Young Kyu Elsevier 2018 Biosensors & Bioelectronics Vol.100 No.-

<P><B>Abstract</B></P> <P>We herein describe novel amine-grafted metal–organic frameworks (MOFs) as a promising alternative to natural peroxidase enzyme and their applications for a fluorescent assay of choline (Cho) and acetylcholine (ACh). Among diverse amine-functionalized MOFs, <I>N</I>,<I>N</I>,<I>N</I>′,<I>N</I>′-tetramethyl-1,4-butanediamine (TMBDA)-functionalized MIL-100(Fe) (TMBDA-MIL-100(Fe)) exhibited the highest peroxidase activity by developing intense fluorescence from Amplex UltraRed (AUR) in the presence of H<SUB>2</SUB>O<SUB>2</SUB>, which was presumably due to the synergetic effect of the enhanced negative potential and precisely controlled molecular size of the grafted diamine. Based on the excellent peroxidase-like activity of TMBDA-MIL-100(Fe), choline and ACh were reliably determined down to 0.027 and 0.036µM, respectively. Furthermore, practical applicability of this strategy was successfully demonstrated by detecting choline and ACh in spiked samples of milk and serum, respectively. This work highlights the advantages of amine-grafted MOFs for the preparation of biomimetic catalysts, extending their scope to biosensor applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Various aliphatic diamines were grafted on coordinatively unsaturated metals sites of MIL-100(Fe) and subjected for peroxidase-like activity. </LI> <LI> Based on the excellent peroxidase-like activity of AFM, a simple and sensitive fluorescent detection of choline and acetylcholine was successfully performed. </LI> <LI> Effectively determined choline and acetylcholine levels in real samples of milk and serum, respectively. </LI> </UL> </P>