랫드에서 인체 재조합 적혈구 조혈인자, rHuEPO의 13주 정맥투여 아만성독성에 관한 연구

김형식,곽승준,천선아,박현선,한하수,임소영,안미영,김원배,김병문,안병옥,홍성렬,이병무 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

A recombinant human erythropoietin (rHuEPO) was administered intravenously at dosage levels of 0, 100, 500, and 2500 IU/㎏/day for a period of 13 weeks. There were no observed clinical signs and deaths related to treatment in all groups tested. Decreases in body weight gain and food consumption were observed only in males of 2,500 IU/㎏ group after 2 weeks. In hematological parameters, erythrocyte content, hematocrit values and hemoglobin concentration were dose-dependently increased in rHuEPO treated groups. The ratio between kidney weight and whole body weight was significantly increased in females of 500 and 2,500 IU/㎏ groups. The spleen weight was also increased in both sexes of 500 and 2,500 IU/㎏ groups. However, the absolute weight change of other organs was not observed. In histopathological examinations, the renal tubular basophilia was observed only in males and females of 2,500 IU/㎏ groups. From these results, it is concluded that the no-observed adverse effect level(NOAEL) of rHuEPO is 100 IU/㎏ in rats in the present study.

유세포 측정을 통한 CD34^(+)세포의 정량방법 비교

양형모,서영훈,엄현석,민창기,김희제,정대철,이종욱,진종율,한치화,김춘추,김학주 대한조혈모세포이식학회 1998 대한조혈모세포이식학회지 Vol.3 No.2

본 연구소에서는 현재 CD34^(+) 세포의 정량에 사용되고 있는 4가지 서로 다른 방법을 가지고 골수에 적용하여 그 결과를 비교하였다. 각각의 방법들이 편리한 점과 불리한 점들을 가지고 있었지만, 통계적으로는 유의한 차이를 보이지 않았다. 1) CD34-PE/CD45-FITC 방법13(ISHAGE: International Society of Hematotherapy and Graft Engineering), 2) CD34-PE/CD14-FITC 방법, 3) CD34-PE/CD14-FITC/CD45-PerCP 방법, 4) DNA dye/CD34-PE/CD45-PerCP4(Becton Dickinson) 등을 비교하였으며 그 결과 CD34^(+) 세포의 농도는 다음과 같았다. 1) 0.473±0.345, (%Mean±SD, N=70) 2) 0.663±0.519, (N=20), 3) 0.543±0.381 (N=46), 4) 0.624±0.341, (N=32). 시료로는 여의도 성모병원 카톨릭 조혈모세포이식 센터에서 채혈한 골수를 이용하였다. Four different methods for flow cytometric quantitation of CD34+ cell were compared using bone marrow samples (n=168). Following combination of antibodies were used for the analysis : A) CD45-FITC/CD34-PE (n=70), B) CD14-FITC/CD34-PE (n=20), C) CD14-FITC /CD34-PE /CD45-PerCP(n=46), D) DNA dye/CD34-PE/CD45-PerCP (n=32). Each method showed no significant differences among them (P=0.126, ANOVA test, SPSS Version 7.5). When we compare these methods using same samples (n=12), the P value became 0.832. The mean % of CD34+ cells calculated in this experiment were A) 0.474%, B) 0.663%, C) 0.548%, D) 0.624% respectively. In our laboratory, we decided to use CD45-FITC/CD34-PE methods as a routine protocol.

양식 은어의 미포자충 감염예에 대한 병리조직학적 관찰

조병열,강형길,강효주,류갑민,이재영,박남규,허민도 한국어병학회 2003 한국어병학회지 Vol.16 No.1

1998년 9월 말경, 경남 지역의 양식 은어(Plecoglossus altivelis)에서 미포자충증이 발생하였다. 채집 당시, 하루 약 200마리씩의 폐사가 10일째 진행되고 있었으며 약 10%의 누적폐사율을 나타내었다. 병어는 입올림을 하거나 기면 상태에 있었으며, 대부분 체색흑화 및 복부팽만 소견을 보이고 있었다. 아가미, 아가미 뚜껑, 각종 내장, 복강벽 및 생식소에 직경 1~3㎜의 흰색 결절이 다수 형성되어 있었다. 감염 어종, 기생충의 형태 및 xenoma 분포 장기의 다양성에 근거하여 Glugea plecoglossi에 의한 감염증으로 추정되었다. 병리조직학적 검사를 실시한 결과, 광범위한 장기에 걸쳐 xenoma를 형성하고 있었으나 xenoma 인접조직에 변성 변화는 없었다. 아가미 새변, 비장, 두신 및 체신의 조혈영역에 심한 울혈 소견이 인정되었고, 간장, 심근 및 신세뇨관 국소에는 응고 내지 액화괴사 소견이 확인되었다. 따라서, xenoma의 인접조직에 대한 물리화학적인 영향보다는 xenoma형성 장기 및 조직에 야기된 국소 순환장애가 은어의 폐사와 직접적인 관련을 갖는 것으로 사료되었다. On September in 1998, a microsporidian infection was recognized in ayu, Plecoglossus altivelis, farmed on Kyongnam province of South Korea. Cumulative mortality was around 10% in 10 days. Infected fish which were piping for air near the surface of the water or in the asphyxic, lethargic condition revealed darkening of body and abdominal distention. Numerous whitish nodules up to 3㎜ in size were observed throughout most of body organs and tissues including gill, operculum, peritoneal wall and organs. Xenomas were also histologically confirmed in multiple internal organs with the evidences suggesting circulatory disturbance. Based on the morphology of spore and xenoma, and the distribution of xenomas in organs and tissues, this disease was diagnosed to be a microsporidiosis caused by Glugea plecoglossi. The mortality might be deeply related to the local circulatory disturbance by xemonas rather than the mechano-chemical effect of xenomas on adjacent tissues.

입원 중인 베트남 참전 군인의 삶의 만족도와 관련된 요인

김애리,박종,김율,노희송,박광희,김은숙,김형철,홍강식,류소연,강명근,김기순 朝鮮大學校 附設 醫學硏究所 2007 The Medical Journal of Chosun University Vol.32 No.2

Background and Objectives: The aim of the study was to identify the factors associated with life satisfaction of hospitalized Vietnam veterans. Material and Methods: The data were collected from 200 hospitalized Vietnam veterans of 5 veterans hospitals in Korea from September 13 to 23, 2004. Information of general characteristics, health behavior, disease history, family function, depression and life satisfaction were collected by structured questionnaire. Results: The mean of life satisfaction was 21.48(±6.03), and the mean of depression was 53.10(±9.64). The prevalence of depression was mild depression 24.0%, moderate depression 43.5% and severe depression 25.0%. Depression was associated with life satisfaction and depression was higher, life satisfaction was lower. Family function and age were positively associated with life satisfaction, Conclusion: Life satisfaction was affected by depression and family function in hospitalized Vietnam veterans. Therefore, it was thought that psychosocial approaches such as improve depression and family function in care of hospitalized Vietnam veterans is required.

보신 관광에서 감염된 수입성 Sparganosis 1예 : Intake of Thailand Snake during Trip

서환조,박명재,고경식,백영한,조유정,양현종,류경남,정형근,전정열 대한감염학회 1992 감염 Vol.24 No.1

Human sparganosois was reported more than 100 cases in Korean population. However no case reported yet in Korea as a patient was infected by sparganum from other geographical area, such as Thailand. The case we are reported here is a 38 year-old Korean male who had been suffered from mass being a small, round and soft consistance in upper portion of his right thigh. The patients stated that he had an opportunity to eat living snake in Bangkok, Thailand during trip. As therapy praziquantel (75㎎/㎏/day) was given p.o. for 14 days, but in vain to cure. Following medical treatment, surgical exicision was performed to remove a alive, soft, whitish-milky, mobile and elongated sparganum. Serlogical test by micro-ELISA for sparganum-specific antibody revealed a high serum antibody level of absorbance 0.67 (positive criterion: absorbance 0.22).

백혈병 마우스 모델의 동종골수이식에서 활성화된 자연살해세포들의 보충이 이식편대백혈병효과와 이식편대숙주반응에 미치는 영향

엄현석,한치화,박수정,김소연,정낙균,정대철,진종률,최일봉,양형모,서영훈,송현근,최인표,민우성,김춘추 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: 백혈병에서 동종골수이식 (allogeneic bone marrow transplantation)의 성공적 치료 효과를 얻기 위해서는 이식편대숙주반응 (graft-versus-host disease, GVHD) 발생의 극복과 재발의 방지가 중요한 과제이다. 골수를 역류원심성 세포분리 (counterflow centrifugal elutriation, CCE) 방법으로 분리하여 얻은 rotor off (R/O) 세포분획은 T 세포의 수는 적지만 조혈모세포들을 다량 포함하고 있어 동종골수이식에서 주조직적합복합체 (major histocompatibility complex, MHC) 차이를 극복할 수 있고, 이식편의 생착 성공과 GVHD 발생 예방에 효과적이다. 그러나 골수로부터 T 세포를 제거하면 백혈병세포를 공격하는 이식편대백혈병 (graft-versus-leukemia, GVL) 효과가 감소되기 때문에 백혈병 재발의 빈도가 높다. 자연살해세포 (natural killer cell, NK cell)의 보충 첨가는 동종골수이식 후 GVHD 발생을 줄이면서 충분한 GVL 효과를 얻을 수가 있다. 따라서 저자는 분리 후 IL-2로 활성화시킨 NK 세포들을 골수 R/O 세포분획과 함께 백혈병 마우스 모델에 동종이식함으로써 GVHD와 GVL에 미치는 효과를 관찰하였다. 방법: Balb/c (H-2^(d)) 마우스에서 유래된 A20 (murine B-lymphoma/leukemia cell line, H-2^(d)) 백혈병 세포를 이식 2 일 전에 Balb/c 마우스에 주입하고, 치사량의 전신 방사선을 조사한 직후에 Balb/c 또는 C57BL/6 (H-2^(b)) 마우스의 골수 R/O 세포분획을 꼬리정맥을 통하여 주입하였다. 이들은 모두 이식 후 6-8 주 이내에 사망하였다. 동종이식의 대조군 (n=9)에는 1 × 10^(7)의 R/O 세포분획만을 주입하였고, 실험군 (n=9)에는 C57BL/6 마우스의 비장세포들로부터 단클론항체들을 이용한 negative selection방법으로 분리한 후 IL-2로 활성화된 5 × 10^(5)의 NK 세포분획을 1 × 10^(7)의 R/O 세포분획과 함께 주입하였다. GVL 효과의 판정은 이식 후 14 일과 28 일 째 되는 날 마우스에서 골수, 비장, 간 등을 얻어 백혈병 세포들의 침윤을 조직학적으로 관찰하였으며, GVHD의 정도는 육안적 관찰법으로 평가하였다. 결과: R/O 세포분획만을 이식한 대조군의 골수, 비장, 그리고 간 조직에서는 A20 백혈병 세포의 침윤이 각각 89% (8/9), 78% (7/9)와 22% (2/9)에서 관찰되었고, R/O 세포분획과 NK 세포분획을 함께 이식한 실험군에서는 비장과 간을 제외한 골수에서만 89% (8/9)에서 A20 백혈병 세포의 침윤이 관찰되어 두 군 사이에 장기별 분포의 차이를 볼 수 있었다 (P= 0.0001). 한편 GVHD는 두 군 모두에서 경하게 나타나서 유의한 차이는 없었다. 또한 생착 부전으로 사망한 마우스는 없었다. 결론: CCE를 이용하여 T 세포를 제거한 동종골수이식에서 NK 세포의 보충은 GVHD의 악화는 일으키지 않으면서, 백혈병의 진행을 억제하는 GVL 효과를 얻을 수 있었다. Background: Allogeneic bone marrow transplantation (BMT) with T cell-depleted marrow accompanies engraftment failure and relapse of leukemia by a loss of the graft-versus-leukemia (GVL) effect frequently, while it can prevent GVHD. Supplement of NK cells could prevent GVHD and enhance GVL effect in several murine allogeneis BMT models Roter off (R/O) cell fraction obtained by counterflow centriation elutriatio (CCO) contains small number of T cells and many hematopoietic stem cells. The aim of this study was to determine the effect of R/O cell fraction supplemented with IL-2 activated NK cells on GVL and GVHD within the leukemic mouse BMT model. Methods: Inoculation of A20 (H-2d, murine B-lymphoma/leukemia, Balb/c origin) cells into Balb/c mice via the tail vein 2 days prior to lethal total body irradiation (TBI) and infusion of the Balb/c BM or C57BL/6 (H-2b) R/O fraction were performed. It resulted in 100% mortality within 6 to 8 weeks. The irradiated mice in the control group were injected with 1 × 107 R/O cell fraction alone (n=9) and in the experimental group mice were injected with 1 × 107 R/O cell fraction plus 5 × 105 negatively selected IL-2 activated NK cell fractions of the spleens via the tail vein (n=9). On day 14 and 28 after BMT, the bone marrows, spleens, and livers of mice were harvested for histopathologic analysis of the infiltrations of leukemic cells. We then evaluated the GVHD within the mice. Results: A histopathologic study of the recipients receiving R/O fraction alone showed infiltration of leukemic cells, 89% (8/9) in bone marrows, 78% (7/8) in spleens, and 22% (2/9) in livers. The experimental group of mice showed only the infiltration of leukemic cells 89% (8/9) in bone marrows, not in spleens and livers. There were the organ differences of the leukemic cells infiltrations between the two groups (P=0.0001). There were no obvious differences in the GVHD scores between these two groups, and severe GVHD was not observed. There was no engraftment failure among groups. Conclusion: Thus, our findings suggest that R/O cell fraction obtained by CCE and supplemented with NK cells can promote GVL effect without mediating clinically overt GVHD in allogeneic BMT of mouse leukemia.

Controllable n-doping of molybdenum disulfide on phosphosilicate glass

Hyung-Youl PARK,Jin-Hong PARK 한국진공학회 2016 한국진공학회 학술발표회초록집 Vol.2016 No.8

Unstable Pathologic Vertebral Fractures in Multiple Myeloma : Propensity Score Matched Cohort Study between Reconstructive Surgery with Adjuvant Radiotherapy and Radiotherapy Alone

Hyung-Youl Park,Young-Hoon Kim,Joo-Hyun Ahn,Kee-Yong Ha,Sang-Il Kim,Jae-Woong Jung 대한신경외과학회 2022 Journal of Korean neurosurgical society Vol.65 No.2

Objective : Although radiotherapy (RT) is recommended for multiple myeloma (MM) involving spine, the treatment of choice between reconstructive surgery with RT and RT alone for pathologic vertebral fractures (PVFs) associated with structural instability or neurologic compromises remains controversial. The purpose of this study was to evaluate the clinical efficacies of reconstructive surgery with adjuvant RT for treatment of MM with PVFs by comparing with matched cohorts treated with RT alone. Methods : Twenty-eight patients underwent reconstructive surgery followed by RT between 2008 and 2015 in a single institution, for management of PVFs associated with structural instability of the spine and/or neurologic compromises (group I). Twentyeight patients were treated with RT alone (group II) after propensity score matching in a 1-to-1 format based on instability of the spine, as well as age and performance. Clinical outcomes including the overall survival rates, duration of independent ambulation, neurological status, and numeric rating scale (NRS) for back pain were compared. Results : Clinical and radiological features before treatment were similar in both groups. The median survival period was similar between the two groups. However, the mean duration of independent ambulation was significantly longer in group I (88.8 months; 95% confidence interval [CI], 66.0–111.5) than in group II (39.4 months; 95% CI, 25.2–53.6) (log rank test; p=0.022). Deterioration of Frankel grade (21.4% vs. 60.7%, p=0.024) and NRS for back pain (2.7±2.2 vs. 5.0±2.7, p=0.000) at the last follow-up were higher in the group II. Treatment-related complications were similar in both groups. Conclusion : In patients with unstable PVFs due to MM, reconstructive surgery may yield superior clinical outcomes compared with RT alone in maintaining independent ambulation and neurological status, as well as pain control despite similar median survival and complications.

n- and p-Type Doping Phenomenon by Artificial DNA and M-DNA on Two-Dimensional Transition Metal Dichalcogenides

Park, Hyung-Youl,Dugasani, Sreekantha Reddy,Kang, Dong-Ho,Jeon, Jeaho,Jang, Sung Kyu,Lee, Sungjoo,Roh, Yonghan,Park, Sung Ha,Park, Jin-Hong American Chemical Society 2014 ACS NANO Vol.8 No.11

<P>Deoxyribonucleic acid (DNA) and two-dimensional (2D) transition metal dichalcogenide (TMD) nanotechnology holds great potential for the development of extremely small devices with increasingly complex functionality. However, most current research related to DNA is limited to crystal growth and synthesis. In addition, since controllable doping methods like ion implantation can cause fatal crystal damage to 2D TMD materials, it is very hard to achieve a low-level doping concentration (nondegenerate regime) on TMD in the present state of technology. Here, we report a nondegenerate doping phenomenon for TMD materials (MoS<SUB>2</SUB> and WSe<SUB>2</SUB>, which represent n- and p-channel materials, respectively) using DNA and slightly modified DNA by metal ions (Zn<SUP>2+</SUP>, Ni<SUP>2+</SUP>, Co<SUP>2+</SUP>, and Cu<SUP>2+</SUP>), named as M-DNA. This study is an example of interdisciplinary convergence research between DNA nanotechnology and TMD-based 2D device technology. The phosphate backbone (PO<SUB>4</SUB><SUP>–</SUP>) in DNA attracts and holds hole carriers in the TMD region, n-doping the TMD films. Conversely, M-DNA nanostructures, which are functionalized by intercalating metal ions, have positive dipole moments and consequently reduce the electron carrier density of TMD materials, resulting in p-doping phenomenon. N-doping by DNA occurs at ∼6.4 × 10<SUP>10</SUP> cm<SUP>–2</SUP> on MoS<SUB>2</SUB> and ∼7.3 × 10<SUP>9</SUP> cm<SUP>–2</SUP> on WSe<SUB>2</SUB>, which is uniform across the TMD area. p-Doping which is uniformly achieved by M-DNA occurs between 2.3 × 10<SUP>10</SUP> and 5.5 × 10<SUP>10</SUP> cm<SUP>–2</SUP> on MoS<SUB>2</SUB> and between 2.4 × 10<SUP>10</SUP> and 5.0 × 10<SUP>10</SUP> cm<SUP>–2</SUP> on WSe<SUB>2</SUB>. These doping levels are in the nondegenerate regime, allowing for the proper design of performance parameters of TMD-based electronic and optoelectronic devices (<I>V</I><SUB>TH</SUB>, on-/off-currents, field-effect mobility, photoresponsivity, and detectivity). In addition, by controlling the metal ions used, the p-doping level of TMD materials, which also influences their performance parameters, can be controlled. This interdisciplinary convergence research will allow for the successful integration of future layered semiconductor devices requiring extremely small and very complicated structures.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2014/ancac3.2014.8.issue-11/nn5048712/production/images/medium/nn-2014-048712_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn5048712'>ACS Electronic Supporting Info</A></P>

Wide-Range Controllable n-Doping of Molybdenum Disulfide (MoS₂) through Thermal and Optical Activation

Park, Hyung-Youl,Lim, Myung-Hoon,Jeon, Jeaho,Yoo, Gwangwe,Kang, Dong-Ho,Jang, Sung Kyu,Jeon, Min Hwan,Lee, Youngbin,Cho, Jeong Ho,Yeom, Geun Young,Jung, Woo-Shik,Lee, Jaeho,Park, Seongjun,Lee, Sungjoo American Chemical Society 2015 ACS NANO Vol.9 No.3

<P>Despite growing interest in doping two-dimensional (2D) transition metal dichalcogenides (TMDs) for future layered semiconductor devices, controllability is currently limited to only heavy doping (degenerate regime). This causes 2D materials to act as metallic layers, and an ion implantation technique with precise doping controllability is not available for these materials (<I>e</I>.<I>g</I>., MoS<SUB>2</SUB>, MoSe<SUB>2</SUB>, WS<SUB>2</SUB>, WSe<SUB>2</SUB>, graphene). Since adjustment of the electrical and optical properties of 2D materials is possible within a light (nondegenerate) doping regime, a wide-range doping capability including nondegenerate and degenerate regimes is a critical aspect of the design and fabrication of 2D TMD-based electronic and optoelectronic devices. Here, we demonstrate a wide-range controllable n-doping method on a 2D TMD material (exfoliated trilayer and bulk MoS<SUB>2</SUB>) with the assistance of a phosphorus silicate glass (PSG) insulating layer, which has the broadest doping range among the results reported to date (between 3.6 × 10<SUP>10</SUP> and 8.3 × 10<SUP>12</SUP> cm<SUP><B>-</B>2</SUP>) and is also applicable to other 2D semiconductors. This is achieved through (1) a three-step process consisting of, first, dopant out-diffusion between 700 and 900 °C, second, thermal activation at 500 °C, and, third, optical activation above 5 μW steps and (2) weight percentage adjustment of P atoms in PSG (2 and 5 wt %). We anticipate our widely controllable n-doping method to be a starting point for the successful integration of future layered semiconductor devices.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2015/ancac3.2015.9.issue-3/acsnano.5b00153/production/images/medium/nn-2015-00153b_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn5b00153'>ACS Electronic Supporting Info</A></P>