• IMMUNE NETWORK
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• v.3 no.4
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• pp.287-294
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• 2003

Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.150-155
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• 2003

Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.

• Clinical and Experimental Pediatrics
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• v.56 no.1
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• pp.26-31
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• 2013

Purpose: Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT). Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's posttransplant immune reconstitution, and therefore require investigation. Methods: The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK) cell recovery. The impact of pre- and post-transplant variables, including diagnosis of Epstein-Barr virus (EBV) DNAemia posttransplant, on lymphocyte recovery was evaluated. Results: The lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells, and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of $CD16^+/56^+$ cell recovery. Younger patients showed delayed recovery of both $CD3^+/CD8^+$ and $CD19^+$ cells. EBV DNAemia had a deleterious impact on the recovery of both $CD3^+$ and $CD3^+/CD4^+$ lymphocytes at 1 year post-transplant. Conclusion: In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.

• Journal of Korean Academy of Fundamentals of Nursing
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• v.13 no.3
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• pp.428-436
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• 2006

Purpose: To investigate the levels of uncertainty and anxiety at admission and discharge to the isolation unit for patients undergoing hematopoietic stem cell transplantation (HSCT). Method: The data were collected from 60 patients who were admitted to the department of HSCT. Uncertainty and anxiety were assessed using the Mishel Uncertainty in Illness Scale (MUIS) and Anxiety Inventory (STAI). Collected data were analyzed using the SAS program. Results: The mean score for anxiety at admission was 2.20, and at discharge 2.10. The mean score for uncertainty at admission was 2.19, and at discharge 2.07. The anxiety at admission the group with physical discomfort was higher than that of group without physical discomfort. A positive relationship was found between anxiety and uncertainty at admission and at discharge. The major variables were expectation for cure and physical discomfort, explaining 25.87% of the anxiety at admission. The major variable was expectation for cure, explaining 20.94% of the uncertainty at admission. Conclusion: Front the above results, it can be concluded that support and consideration are required to reduce anxiety of the inpatient in single room.

• Journal of Yeungnam Medical Science
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• v.29 no.2
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• pp.96-101
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• 2012

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the optimal curative treatment for acute myeloid leukemia (AML), but some patients develop bone marrow relapse due to remnant leukemia, and few patients develop extramedullary relapse without bone marrow relapse. Isolated extramedullary relapse (IMER) is defined as extramedullary relapse without bone marrow relapse. IMER has been reported in various sites, including the skin, soft tissue, and central nervous system(CNS). Isolated CNS relapse is relatively rare and is associated with poor prognosis due to the absence of an optimal treatment for it. Reported herein is a case involving an adult AML woman who suffered from isolated extramedullary relapse in the CNS after allogeneic HSCT. She was treated with intrathecal chemotherapy and whole-brain and spine radiotherapy, followed by systemic chemotherapy. She is currently well, with no evidence of leukemia recurrence for over six years.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.63-67
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• 2016

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose ($1{\times}10^6cells/kg$), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.173-180
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• 2006

Purpose : Cytomegalovirus(CMV) infection still remains as a major cause of morbidity and mortality after stem cell transplantation. In this study, we analyzed the results of antigenemia-guided preemptive therapy among children with allogeneic hematopoietic stem cell transplantation to determine the incidence and risk factors associated with CMV antigenemia, and evaluated the efficacy of the CMV antigenemia based preemptive therapy. Methods : We enrolled 213 pediatric patients following allogeneic hematopoietic stem cell transplantation(HSCT), at the Catholic HSCT center between October 1998 and December 2003. Pre-emptive ganciclovir was started when more than 5 CMV Ag-positive cells were detected in matched sibling HSCT, and when any Ag-positive cells were seen in unrelated allogenic HSCT. Results : CMV antigenemia was observed in 88(41.3 percent) of 213 patients on median day 28(day 11-99). In univariated analysis, use of unrelated donors(other than siblings), age of recipient(more than 5 years at transplant) at transplantation, the presence of recipient CMV-IgG before transplantation, TBI-based conditioning regimen and the presence of acute GvHD(grade ${\geq}II$) were the risk factors for positive CMV antigenemia. In multivariate analysis, unrelated bone marrow transplantation, positive recipient CMV serology and acute GvHD(grade ${\geq}II$) were the independent risk factors for positive CMV antigenemia. Conclusion : Risk factors of CMV infection in children were CMV serostatus of the recipient, the source of stem cells, and acute graft-versus-host disease. The pre-emptive therapy based on CMV antigenemia was effective in the prevention of CMV disease.

• Natural Product Sciences
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• v.14 no.2
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• pp.118-121
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• 2008

Manassantin B, a dilignan isolated from Saururus chinensis, significantly inhibited proliferation in HSC-T6 cells in concentration- and time-dependent manners. In addition, treatment of HSC-T6 cells with manassantin B changed cell morphology from flattened myofibroblastic membranous morphology, representing activation state, to slender shape, representing quiescent state. Furthermore, manassantin B effectively reduced collagen content in HSC-T6 cells. These results suggested that manassantin B exerted antifibrotic activity in HSCT6 cells, in part, via inhibition of cell proliferation and decrease of collagen production.

• Journal of KSNVE
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• v.9 no.1
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• pp.113-120
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• 1999

A perforated tube nozzle as an exhaust noise suppressor of a high-speed civil transport(HSCT) is proposed. The experimental results for the near and far field sound. the visualization of jet structures and the static pressure distributions in the jet passing through a perforated tube are presented and discussed in comparison with those for a simple tube. It is shown that the perforated tube has an excellent performance to greatly reduce the shock-associated noise and that also the turbulent mixing noise is reduced in the range of a limited jet pressure ratio. This considerable noise reduction is due to the pressure relief caused by the through-flow through the perforated holes. Such a pressure relief results in the transformation of normal shock waves into weak Mach waves of X -type and increases the thrust force of the perforated tube nozzle.

• The Journal of Aerospace Industry
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• s.70
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• pp.70-93
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• 2008

산업의 고도화에 따라 시간을 절약하고 공간을 활용하기 위한 방법으로서, 보다 큰 항공기, 보다 빠른 항공기에 대한 요구가 꾸준히 제기된다. 최근 불거진 지구온난화에 대한 이슈는 모든 산업의 초점을 친환경으로 돌려고 있어서, 항공기산업의 경우에도 예외 없이 보다 친환경적이고, 연료 효율적인 항공기개발에 집중하고 있다. 또한, 과거에 비해 자유의지가 강조되는 현재에는 보다 이용이 간편한 개인용 항공기의 출현이 요구되고 있어 이 분야에 대한 연구도 활발히 진행 중이다. 이에 따라 많은 국가들이 각각의 요구에 따라 초대형여객기(VLCT), 차세대 초음속여객기(HSCT), 그린항공기, 개인 자가용 항공기(PAV) 등의 형태로 개발을 서두르고 있으며, 일부 분야는 이미 상용화를 눈앞에 두고 있다. 특히 PAV의 수요는 향후에 자동차 시장의 일부를 대체할 것으로 예상되는 만큼 선진국들은 수요자의 요구에 따라 발 빠르게 대응하여 PAV에 대한 투자를 아끼지 않고 있다. 따라서 본 연구에서는 미래형 항공교통수단의 개발전망과 동향을 분석함으로써 앞으로 우리나라 항공기산업의 발전방향에 대한 시사점을 도출하고자 하였다. 특히 틈새 시장으로서의 PAV 분야의 개발동향과 전망을 살펴봄으로써, 동 분야에 대한 연구개발과 투자를 통한 우리나라 항공기산업의 발전기회를 모색해 보고자 하였다.