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Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells

  • Kim, Myung-Ho;Kim, Hee-Hoon;Jeong, Jong-Min;Shim, Young-Ri;Lee, Jun-Hee;Kim, Ye Eun;Ryu, Tom;Yang, Keungmo;Kim, Kyu-Rae;Jeon, Byeong-Min;Kim, Sun Chang;Jung, Jae-Kwang;Choi, Jae-Kap;Lee, Young-Sun;Byun, Jin-Seok;Jeong, Won-Il
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.815-822
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    • 2020
  • Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3+ regulatory T cells (Tregs) increased but IL-17-producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORgt expression and stimulating Foxp3 expression. Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.

Redo CABG Using Various Arterial Grafts (다양한 동맥도관을 이용한 재관상동맥 우회술)

  • Min, Ho-Ki;Lee, Young-Tak;Lee, Min-A;Kim, Wook-Sung;Park, Pyo-Won;Sung, Ki-Ick;Jun, Tae-Gook;Yang, Ji-Hyuk
    • Journal of Chest Surgery
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    • v.42 no.4
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    • pp.456-463
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    • 2009
  • Background: Although the reports on re-operative coronary revascularization (redo-CABG) have increased, there are only limited reports on redo-CABG using arterial grafts. The aim of this study was to analyze the safety and feasibility of using various arterial grafts for redo-CABG. Material and Method: A consecutive series of patients who underwent 33 redo-CABGs from March 2001 to July 2008 were retrospectively reviewed. We performed conventional CABG in 17 patients, on-pump beating CABG in 7, off-pump CABG in 7 and minimally invasive direct coronary artery bypass in 2. The grafted that were used included 34 internal thoracic arteries (ITA), 14 radial arteries, 14 right gastroepiploic arteries and others. Arterial composite grafts were constructed in 26 patients. Of these, a previously patent in-situ left ITA was re-used as the in-flow of a composite graft in 10 patients. Result: No hospital deaths or major wound problems occurred. The post-operative complications included 2 myocardial infarctions (6%), 1 intra-aortic balloon pump insertion (3%), 5 cases of atrial fibrillation (15.1 %) and 3 neurologic complications (9.1%). The meanfollow-up duration was 31.1$\pm$22.7 months and the 3 year survival rate was 86.4%. There were 4 late deaths (2 cardiac deaths) and no recurrent angina during the follow-up period. Conclusion: Redo-CABG with using various arterial grafts is currently a safe, feasible procedure, but further investigation and long term follow-up are needed.

Use of Human Adipose Tissue as a Source of Endothelial Cells (혈관내피세포 채취의 원천으로 인간 지방조직의 활용)

  • Park, Bong-Wook;Hah, Young-Sool;Kim, Jin-Hyun;Cho, Hee-Young;Jung, Myeong-Hee;Kim, Deok-Ryong;Kim, Uk-Kyu;Kim, Jong-Ryoul;Jang, Jung-Hui;Byun, June-Ho
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.4
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    • pp.299-305
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    • 2010
  • Purpose: Adipose tissue is located beneath the skin, around internal organs, and in the bone marrow in humans. Its main role is to store energy in the form of fat, although it also cushions and insulates the body. Adipose tissue also has the ability to dynamically expand and shrink throughout the life of an adult. Recently, it has been shown that adipose tissue contains a population of adult multipotent mesenchymal stem cells and endothelial progenitor cells that, in cell culture conditions, have extensive proliferative capacity and are able to differentiate into several lineages, including, osteogenic, chondrogenic, endothelial cells, and myogenic lineages. Materials and Methods: This study focused on endothelial cell culture from the adipose tissue. Adipose tissues were harvested from buccal fat pad during bilateral sagittal split ramus osteotomy for surgical correction of mandibular prognathism. The tissues were treated with 0.075% type I collagenase. The samples were neutralized with DMEM/and centrifuged for 10 min at 2,400 rpm. The pellet was treated with 3 volume of RBC lysis buffer and filtered through a 100 ${\mu}m$ nylon cell strainer. The filtered cells were centrifuged for 10 min at 2,400 rpm. The cells were further cultured in the endothelial cell culture medium (EGM-2, Cambrex, Walkersville, Md., USA) supplemented with 10% fetal bovine serum, human EGF, human VEGF, human insulin-like growth factor-1, human FGF-$\beta$, heparin, ascorbic acid and hydrocortisone at a density of $1{\times}10^5$ cells/well in a 24-well plate. Low positivity of endothelial cell markers, such as CD31 and CD146, was observed during early passage of cells. Results: Increase of CD146 positivity was observed in passage 5 to 7 adipose tissue-derived cells. However, CD44, representative mesenchymal stem cell marker, was also strongly expressed. CD146 sorted adipose tissue-derived cells was cultured using immuno-magnetic beads. Magnetic labeling with 100 ${\mu}l$ microbeads per 108 cells was performed for 30 minutes at $4^{\circ}C$ a using CD146 direct cell isolation kit. Magnetic separation was carried out and a separator under a biological hood. Aliquous of CD146+ sorted cells were evaluated for purity by flow cytometry. Sorted cells were 96.04% positivity for CD146. And then tube formation was examined. These CD146 sorted adipose tissue-derived cells formed tube-like structures on Matrigel. Conclusion: These results suggest that adipose tissue-derived cells are endothelial cells. With the fabrication of the vascularized scaffold construct, novel approaches could be developed to enhance the engineered scaffold by the addition of adipose tissue-derived endothelial cells and periosteal-derived osteoblastic cells to promote bone growth.

Evaluation of Hemodynamic Failure with Acetazolamide Challenged $^{123}I-IMP$ Brain SEPCT and PET (PET과 Acetazolamide 부하 $^{123}I-IMP$ 뇌혈류 SPECT를 이용한 혈역학적 부전의 평가)

  • Chun, Kyung-Ah;Cho, In-Ho;Won, Kyu-Jang;Lee, Hyung-Woo;Hayashida, Kohei
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.2
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    • pp.94-102
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    • 2003
  • Purpose : Cerebral blood flow (CBF) reactivity to acetazolamide (ACZ) is useful to select patients with hemodynamic failure. However, it is still a matter of speculation that varying degrees of regional CBF increases after ACZ administration represent the severity or stage of regional hemodynamic failure as assessed by positron emission tomography (PET). We studied to elucidate whether ACZ challenge $^{123}I-IMP$ brain single photon emission tomography (SPECT) can accurately grade the seventy of regional hemodynamic failure. Materials and Methods: Eighteen patients (M: 16, F: 2, average age: 61 years) with unilateral occlusive disease of the internal carotid artery or the trunk of the middle cerebral artery (MCA). Patients undewent $^{123}I-IMP$ brain SPECT study with acetazolamide challenge and PET study was carried out within 2 weeks before and after SPECT study. Five healthy volunteers with a mean age of 48 years (range: 28-73 yr, M: 3, F: 2) underwent PET studies to determine normal values. In SPECT study, an asymmetry index (Al)-the percentage of radioactivity of region of interest (ROI) in the occlusive cerebrovascular lesion to the contralateral homologous ROI-was used for numerical evaluation of relative $^{123}I-IMP$ distribution. In PET study, regional CBF, oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen ($CMRO_2$) and cerebral blood volume (CBV) values were measured with $^{15}O-labeled$ gas inhalation method and the values were used for comparison with Al (Al during acetazolamide challenge-Al of basal study) on the SPECT study. ROls were classified by severity into three groups (normal, stage I and stage II). Results: Mean values of Al in areas with normal, stage I and stage II hemodynamic failure were $6.25{\pm}7.77%\;(n=107),\;-10.38{\pm}10.41%\:(n=117)\;and\;13.30{\pm}10.51%\;(n=140)$, respectively. Al significantly differed with each groups (p<0.05). Correlation between Al and CBF, OEF and CBV/CBF in hemisphere with occlusive cerebrovascular lesion was 0.20 (p<0.01), -0.28 (p<0.01) and -0.28 (p<0.01), respectively. Conclusion: We concluded that $^{123}I-IMP$ brain SPECT with acetazolamide challenge could determine the severity ad stage of regional hemodynamic failure as assessed by PET.

The Clinical Experiences of Patch Angioplasty in Isolated Critical Left Main Coronary Artery Stenosis (첨포를 이용한 좌주관상동맥 협착증의 치료)

  • 윤치순;유경종;이교준;김대준;강면식
    • Journal of Chest Surgery
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    • v.31 no.7
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    • pp.674-678
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    • 1998
  • The conventional surgical treatment of isolated critical stenosis of the left main coronary artery restores a less physiologic perfusion of the myocardium, leads to occlusion of the left coronary ostium, and consumes an appreciable length of bypass material. From June 1994 to February 1996, eleven patients, three male and eight female, underwent patch angioplasty and additional bypass graft to left anterior descending artery (10 internal mammary artery, 1 saphenous vein) in isolated critical left main coronary artery stenosis. Their ages ranged from 34 to 62 years, mean 44 years. All had 60% to 90% stenosis of the left main coronary artery and Class III angina. The angiogram showed nine osteal lesion and three main stem stenosis. The operation was performed with conventional cardiopulmonary bypass and cold blood cardioplegia. We approached anteriorly and used bovine pericardium as onlay patch in all patients. There were one leg wound dehiscence, but no operative deaths and infarctions. All patients are free of symptoms after a mean follow-up of 15.5 months. Angiographic restudy at an average 14.4 months was obtained in five patients and showed widely patent left main coronary artery with excellent runoff. But additional graft to left anterior descending coronary artery were stenosed in two patients and showed diminutive flow in others. Our preliminary results suggest that angioplasty of the left main coronary artery can be carried out with low operative risks. But additional bypass graft to left anterior descending coronary artery may be unnecessary. The technique appears to be a promising alternative to conventional coronary artery bypass grafting in isolated left main coronary artery stenosis.

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Rectal Temperature Maintenance Using a Heat Exchanger of Cardioplegic System in Cardiopulmonary Bypass Model for Rats (쥐 심폐바이패스 모델에서 심정지액 주입용 열교환기를 이용한 직장체온 유지)

  • Choi Se-Hoon;Kim Hwa-Ryong;Paik In-Hyuck;Moon Hyun-Jong;Kim Won-Gon
    • Journal of Chest Surgery
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    • v.39 no.7 s.264
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    • pp.505-510
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    • 2006
  • Background: Small animal cardiopulmonary bypass (CPB) model would be a valuable tool for investigating path-ophysiological and therapeutic strategies on bypass. The main advantages of a small animal model include the reduced cost and time, and the fact that it does not require a full scale operating environment. However the rat CPB models have a number of technical limitations. Effective maintenance and control of core temperature by a heat exchanger is among them. The purpose of this study is to confirm the effect of rectal temperature maintenance using a heat exchanger of cardioplegia system in cardiopulmonary bypass model for rats. Material and Method: The miniature circuit consisted of a reservoir, heat exchanger, membrane oxygenator, roller pump, and static priming volume was 40 cc, Ten male Sprague-Dawley rats (mean weight 530 gram) were divided into two groups, and heat exchanger (HE) group was subjected to CPB with HE from a cardioplegia system, and control group was subjected to CPB with warm water circulating around the reservoir. Partial CPB was conducted at a flow rate of 40 mg/kg/min for 20 min after venous cannulation (via the internal juglar vein) and arterial cannulation (via the femoral artery). Rectal temperature were measured after anesthetic induction, a ter cannulation, 5, 10, 15, 20 min after CPB. Arterial blood gas with hematocrit was also analysed, 5 and 15 min after CPB. Result: Rectal temperature change differed between the two groups (p<0.01). The temperatures of HE group were well maintained during CPB, whereas control group was under progressive hypothermia, Rectal temperature 20 min after CPB was $36.16{\pm}0.32^{\circ}C$ in the HE group and $34.22{\pm}0.36^{\circ}C$ in the control group. Conclusion: We confirmed the effect of rectal temperature maintenance using a heat exchanger of cardioplegia system in cardiopulmonary bypass model for rats. This model would be a valuable tool for further use in hypothermic CPB experiment in rats.

Study on the Consequence Effect Analysis & Process Hazard Review at Gas Release from Hydrogen Fluoride Storage Tank (최근 불산 저장탱크에서의 가스 누출시 공정위험 및 결과영향 분석)

  • Ko, JaeSun
    • Journal of the Society of Disaster Information
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    • v.9 no.4
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    • pp.449-461
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    • 2013
  • As the hydrofluoric acid leak in Gumi-si, Gyeongsangbuk-do or hydrochloric acid leak in Ulsan, Gyeongsangnam-do demonstrated, chemical related accidents are mostly caused by large amounts of volatile toxic substances leaking due to the damages of storage tank or pipe lines of transporter. Safety assessment is the most important concern because such toxic material accidents cause human and material damages to the environment and atmosphere of the surrounding area. Therefore, in this study, a hydrofluoric acid leaked from a storage tank was selected as the study example to simulate the leaked substance diffusing into the atmosphere and result analysis was performed through the numerical Analysis and diffusion simulation of ALOHA(Areal Location of Hazardous Atmospheres). the results of a qualitative evaluation of HAZOP (Hazard Operability)was looked at to find that the flange leak, operation delay due to leakage of the valve and the hose, and toxic gas leak were danger factors. Possibility of fire from temperature, pressure and corrosion, nitrogen supply overpressure and toxic leak from internal corrosion of tank or pipe joints were also found to be high. ALOHA resulting effects were a little different depending on the input data of Dense Gas Model, however, the wind direction and speed, rather than atmospheric stability, played bigger role. Higher wind speed affected the diffusion of contaminant. In term of the diffusion concentration, both liquid and gas leaks resulted in almost the same $LC_{50}$ and ALOHA AEGL-3(Acute Exposure Guidline Level) values. Each scenarios showed almost identical results in ALOHA model. Therefore, a buffer distance of toxic gas can be determined by comparing the numerical analysis and the diffusion concentration to the IDLH(Immediately Dangerous to Life and Health). Such study will help perform the risk assessment of toxic leak more efficiently and be utilized in establishing community emergency response system properly.

Predictive Values of Early Rest/24 Hour Delay T1-201 Perfusion SPECT for Wall Motion Improvement in Patients with Acute Myocardial Infarction After Reperfusion (급성 심근 경색 환자에서 재관류 후 조기에 시행한 휴식/24시간 지연 T1-201 심근 SPECT의 심근벽 운동 호전 예측능)

  • Hyun, In-Young;Kwan, June
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.3
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    • pp.259-265
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    • 1998
  • Purpose: We studied early rest/24 hour delay T1-201 perfusion SPECT for prediction of wall motion improvement after reperfusion in patients with acute myocardial infarction. Materials and Methods: Among 17 patients (male/female= 11/6, age: $59{\pm}13$) with acute myocardial infarction, 15 patients were treated with percutaneous transcoronary angioplasty (direct:2, delay: 11) and intravenous urokinase (2). Spontaneous resolution occurred in infarct-related arteries of 2 patients. We confirmed TIMI 3 flow of infarct-related artery after reperfusion in all patients with coronary angiography. We performed rest T1-201 perfusion SPECT less then 6 hours after reperfusion and delay T1-201 perfusion SPECT next day. T1-201 uptake was visually graded as 4 point score from normal (0) to severe defect (3). Rest T1-201 uptake ${\le}2$ or combination of rest T1-201 uptake ${\le}2$ or late reversibility were considered to be viable. Myocardial wall motion was graded as 5 point score from normal (1) to dyskinesia (5). Myocardial wall motion was considered to be improved when a segment showed an improvement ${\ge} 1$ grade in follow up echo compared with the baseline values. Results: Among 98 segments with wall motion abnormality, the severity of myocardial wall motion decrease was as follow: mild hypokinesia: 18/98 (18%), severe hypokinesia: 28/98 (29%), akinesia: 51/98 (52%), dyskinesia: 1/98 (1%). The wall motion improved in 85%. Redistribution (13%), and reverse redistribution (4%) were observed in 24 hour delay SPECT. Positive predictive value (PPV) and negative predictive value (NPV) of combination of late reversibility and rest T1-201 uptake were 99%, and 54%. PPV and NPV of rest T1-201 uptake were 100% and 52% respectively. Predictive values of combination of rest T1-201 uptake and late reversibility were not significantly different compared with predictive values of rest T1-201 uptake only. Conclusion: We conclude that early T1-201 perfusion SPECT predict myocardial wall motion improvement with excellent positive but relatively low negative predictive values in patients with acute myocardial infarction after reperfusion.

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Artifactual Perfusion Defects due to the Parameters of Reconstruction Filter in Tc-99m-MIBI Myocardial SPECT Images (Tc-99m-MIBI 심근 SPECT 영상에서 재구성 필터에 의한 인위적 관류결손에 관한 연구)

  • Kwark, Cheol-Eun;Lee, Kyung-Han;Lee, Dong-Soo;Park, Yong-Woo;Chung, June-Key;Lee, Myung-Chul;Seo, Joung-Don;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.1
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    • pp.41-47
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    • 1995
  • Tc-99m-MIBI(Sestamibi) myocardial SPECT along with T1-201 tomographic imaging has demonstrated wide application and high image qualify sufficient for the diagnosis of myocardial perfusion defect, which consequently reflects regional myocardial blood flow, The qualitative values of myocardial SPECT with Tc-99m-MIBI as well as the quantitative cases depend in some degree on the reconstruction techniques of multiple projections. Filtered backprojection(FBP) is the common standard for reconstruction rather than the complicated and time-consuming arithmetic methods. In FBP it Is known that the distribution of radioactivity in reconstructed transverse slices varies with the selected filter parameters such as cutoff frequencies and order(Butterworth case). The cutoff frequencies basically remove and decrease the true radioactive distribution and alter the pixel counts, which lead to underestimation of true counts in specific myocardial regions. In this study, we have investigated the effect of cutoff frequencies of reconstruction filter on the artifactually induced perfusion defects, which are often demonstrated near inferior and/or inferoseptal cardiac walls due to the intense hepatic uptake of Tc-99m-MIBI. A computerized method for identifying the relative degree of artifactual perfusion defect and for comparing those degrees along with the relative amount of hepatic uptake to myocardium was developed and patient images were studied to observe the quantitative degree of underestimation of myocardial perfusion, and to propose some reasonable thresh-old of cutoff frequency in the diagnosis of perfusion defect quantitatively. We concluded that from the quantitative viewpoint cutoff frequencies may be used as high as possible with the sacrifice of homogeneity of image quality, and those frequencies lower than the common 0.3 Nyquist frequency would reveal severe degradation of radio-active distribution near inferior and/or Inferoseptal myocardium when applying Butterworth or low pass filter.

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Quantitative determination of inosine 5'-monophosphate dehydrogenase activity in human peripheral blood mononuclear cells by ion-pair reversed-phase high-performance liquid chromatography (이온쌍 역상 HPLC를 이용한 인체 말초혈액단핵구에서 이노신 5'-일인산 탈수소효소 활성의 정량적 측정)

  • Shin, Hye-Jin;Kwon, Soon-Ho;Park, Ji-Myeong;Kwon, Soon-Hyo;Lee, Kyoung-Ryul;Kim, Young-Jin;Lee, Sang-Hoo
    • Analytical Science and Technology
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    • v.23 no.6
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    • pp.531-536
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    • 2010
  • A quantitative analytical method has been established for the measurement of inosine 5'-monophosphate dehydrogenase (IMPDH) activity in human peripheral blood mononuclear cells (PBMCs) by ion-pair reversed-phase high performance liquid chromatography equipped with ultraviolet detection (HPLC/UV). IMPDH is a ${\beta}$-nicotinamide adenine dinucleotide hydrate (NAD+)-dependent dehydrogenase in which the enzyme converts inosine 5'-monophosphate (IMP) into xanthosine 5'-monophosphate (XMP). Its activity was measured by quantifying a HPLC chromatogram corresponding to XMP produced during the incubation of lysed PBMCs with IMP as a substrate and $NAD^+$ as a coenzyme. XMP produced was detected at a wavelength of 260 nm. The mobile phase was composed of a mixture of 37 mM potassium dihydrogen phosphate containing 7 mM tetra-n-butylammonium hydrogen sulfate adjusted to pH 5.5 and methanol (85:15, v/v) with a flow rate of 1 mL/min. The calibration curve was linear ($r^2$=0.999999) in the range of $0.2-50.0\;{\mu}M$ and the limit of quantification (LOQ) was $0.2\;{\mu}M$. The intra- and inter-day precisions were between 0.88-1.47% and 0.85-5.24%, respectively. The intra- and inter-day accuracies were between 98.74-99.99% and 99.95-101.65%, respectively. IMPDH activity in 11 Korean healthy volunteers ranged from 18.29 to 36.60 nmol/h/mg protein (mean = $27.70{\pm}6.28\;nmol/h/mg$ protein).