• IMMUNE NETWORK
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• v.11 no.1
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• pp.68-78
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• 2011

Background: Graft-versus-host disease (GVHD) is a huddle for success of hematopoietic stem cell transplantation. In this study, effects of irradiation dose on immune kinetics of GVHD were investigated using B6 ${\rightarrow}$ BALB.B system, a mouse model for GVHD after MHC-matched allogeneic transplantation. Methods: BALB.B mice were transplanted with bone marrow and spleen cells from C57BL/6 mice after irradiation with different doses. Leukocytes residing in the peripheral blood and target organs were collected periodically from the GVHD hosts for analysis of chimerism formation and immune kinetics along the GVHD development via flow cytometry. Myeloid cells were tested for production of IL-17 via flow cytometry. Results: Pre-conditioning of BALB.B hosts with 900 cGy and 400 cGy resulted in different chimerism of leukocytes from the blood and affected survival of GVHD hosts. Profiles of leukocytes infiltrating GVHD target organs, rather than profiles of peripheral blood leukocytes (PBLs), were significantly influenced by irradiation dose. Proportions of IL-17 producing cells in the infiltrating $Gr-1^+$ or $Mac-1^+$ cells were higher in the GVHD hosts with high does irradiation than those with low dose irradiation. Conclusion: Pre-conditioning dose affected tissue infiltration of leukocytes and cytokine production by myeloid cells in the target organs.

• Journal of Oral Medicine and Pain
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• v.25 no.2
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• pp.159-165
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• 2000

Subsequent to an allogenic stem cell transplantation(ASCT) on patients with hematologic malignancy(AML, ALL, CML, multiple myeloma, lymphoma etc.), chronic GVHD(graft versus host disease), which is an immunological reaction, occurs. With treatment results from patients who were diagnosed with ALL(acute lymphocytic leukemia), undergone BMT(bone marrow transplantation) and showed oral and skin lesions due to GVHD, treatment of oral manifestations of leukemia and its general management were studied. 90% of patients with chronic GVHD show change in the oral mucosa causing oral manifestations such as leukoplakia, lichenoid change of the oral mucosa, mucosal atrophy, erythema, ulceration and xerostomia. In treating GVHD, extensive systemic immunosuppression cause bacterial, viral, fungal infection that are fatal, and even if the treatment is successful, the patient is already in a severe immunosuppressed state. Therefore, localized target therapy is preferred. In another words, topical application(rinse, cream, ointment etc.) of cyclosporin and steroid in treating oral chronic GVHD is highly recommended, and the use of PUVA(Psoralen Ultraviolet A) and thalidomide is reported to be effective. In treating such diseases, dental treatment to control pain and prevent secondary infection of oral manifestations is very important. To those patients with systemic diseases who show limited effect by general dental treatment, non-invasive treatment such as the dental laser, in addition to the use of drugs, may be necessary to actively treat pain and help the healing process. For greater results, new effective methods are to be developed for treatment.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.595-606
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• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

• IMMUNE NETWORK
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• v.7 no.3
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• pp.149-157
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• 2007

Background: The microsatellites within human leukocyte antigen (HLA) region show considerable polymorphism and strong linkage disequilibrium (LD) with HLA alleles. These microsatellites have been used for genetic analysis including disease mapping to understand susceptibility to autoimmune and infectious diseases. Also, use of microsatellites has recently been proposed as an approach for identifying non-HLA markers within the HLA region that could function as transplantation determinants and for the selection of potential donors for transplantation. Methods: To analyse the frequency of five microsatellites in the Korean population, genotyping for polymorphisms at five microsatellites markers (BAT2, MIB, DQCAR, D6S105 and TNFd) within HLA region was performed on 143 healthy Korean controls. Results: The most frequent genotype shown in healthy Korean controls were BAT2 8 (153 bp, 42.7%), MIB 1 (326 bp, 40.6%), DQCAR 3 (188 bp, 38.5%), D6S105 7 (126 bp, 58.0%) and TNFd 3 (128 bp, 58.0%). And common two-loci haplotypes were found as MIB 1-HLA-B*62 (HF: 10.6%), MIB 6-HLA-B*44 (HF: 7.8%), DQCAR 3-HLA-DRB1*13 (HF: 8.5%), TNFd 5-HLA-B*62 (HF: 7.8%) and D6S105 7-HLA-A*02 (HF: 16.2%). Conclusion: These data might provide useful information on the microsatellites markers with HLA region in Korean population and be helpful in further defining the clinical impact of these microsatellites.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.40-47
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• 2011

Purpose : Norovirus infection, a common cause of community-acquired gastroenteritis, can also lead to severe illness in immunocompromised patients. We investigated clinical manifestations of norovirus infection in pediatric cancer patients. Methods : Stool specimens were collected from pediatric patients with gastrointestinal symptoms between November 2008 and September 2009 at Samsung Medical Center, Seoul, Korea. Norovirus infection was identified by reverse-transcription polymerase chain reaction (RT-PCR). A retrospective chart review was performed in pediatric cancer patients who were diagnosed with norovirus infection. Results : Ten patients were diagnosed with norovirus infection by RT-PCR in stool samples. The median age was 0.83 years (range 0.25-5.5 years) and the male to female ratio was 1.5:1 (6 males and 4 females). Underlying diseases were hematologic malignancies (4/10, 40%), neuroblastoma (4/10, 40%), and brain tumors (2/10, 20%). Three patients were infected before hematopoietic cell transplantation (HCT) and four patients after HCT. All patients had diarrhea (10/10, 100%), with a median frequency of diarrhea of 8.5 times/day (range 4-22 times/day). Median virus shedding duration was 72.5 days (range 19-299 days). Four patients with pneumatosis intestinalis were conservatively treated with bowel rest and total parenteral nutrition. One patient with severe diarrhea and bloody stool had concomitant chronic gut graft-versus-host disease (GVHD). Norovirus infection-related mortality was not observed. Conclusion : Norovirus infection can cause significant clinical manifestations with prolonged viral shedding in immunocompromised patients. Norovirus should be considered in pediatric cancer patients with severe gastrointestinal symptoms.

• 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.

• Radiation Oncology Journal
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• v.32 no.3
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• pp.198-207
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• 2014

Purpose: To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. Materials and Methods: From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. Results: The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). Conclusion: The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

• Journal of Korean Academy of Nursing
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• v.30 no.2
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• pp.514-526
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• 2000

The active treatment phase in preparation for bone marrow transplantation(BMT) of che- motherapy regimen and total body irradiation (TBI) containing regimen requires considerable teaching. There have been researches that are related to treatment onto BMT patients and to psychological change during BMT process. However, it was hard to find researches focused on learning needs of patients undergoing BMT. The purpose of this study was to provide the basic data for effective educational program about BMT by investigating the learning needs in patients undergoing BMT. The subjects consisted of 90 BMT patients have been admitted to the department of BMT at three university hospitals. Data were obtained from October 1998 to March 1999 and analyzed by SAS program for unpaired t-test, ANOVA, Duncan test. The results were as follows : 1. Learning needs related to demographic characteristics was identified as below. That of male was higher than that of female. That of under age 29, unmarried, religious and university graduated group was higher than that of opposite group but it didn't show significant difference. Learning needs of group of patients who were employed was significantly higher then that of unemployed patients. 2. According to types of diagnosis, learning needs of myelodysplastic syndrome(MDS) patients was the higher than that of others, but admission frequency was the least. Learning needs of unrelated matched BMT(UBMT) patients was higher than that of autologous BMT patients. However, it didn't show significant difference. With regard to learning needs according to process of BMT, learning needs of Pre- BMT period or Post-BMT period was significantly higher than that of BMT day. 3. Learning needs related to BMT was relatively high (total mean: 3.11 of 4.0). The order of the mean score of leaning needs was shown as follows : Restricted activities after discharge, Relapse symptom, Complications of BMT, Kinds of available drugs at home. Therefore the learning needs that is related to life after discharge and to relapse and complications after BMT was high. 4. Learning needs related to radiation therapy was high (total mean: 3.35 of 4.0). The learning needs in radiation therapy items was the Skin care of radiation therapy and Purpose of radiation therapy. 5. Learning needs related to graft versus host disease(GVHD) therapy was high (total mean: 3.55 of 4.0). The highest learning needs in GVHD therapy items was the Preventive method GVHD. less admission frequency and UBMT patients. It is necessary that education for BMT patients should be focused on life after discharge and on relapse and complications after BMT. Especially education for allogeneic BMT patients should be emphasized on GVHD. For all of these, it is necessary to develop systematic and concrete educational program.

• Radiation Oncology Journal
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• v.10 no.2
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• pp.247-253
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• 1992

Between August 1987 and July 1991, 22 patients with acute nonlymphocytic leukemia have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. Of these patients, 12 patients were in first complete remission (CR) and 10 patients in second CR or greater or in relapse. All patients were treated with a preparative regimen consisting of cyclophosphamide (CTX, 60 mg/kg) or combined drugs, and 850 cGy single-dose or $150\~200$ cGy fractionated total body irradiation (TBI) administered twice daily for a total dose of $1200\~1320$ cGy. Survivors have been followed from 8 to 64.5 months (median, 24 months). The overall 2 year survival rate, relapse rate and incidence of radiation pneumonitis and graft versus host disease (GVHD) have been evaluated by age, phase of disease, initial WBC count, modality of TBI or conditioning chemotherapy. Overall 2 year survival was $58{\%}$. The median survival was 31 months and mean survival was 23.2 months. Overall survival have significant impact in patients of age >19 years old (p=0.008), patients in first CR (p=0.09). Two year survival rate is significantly correlated with age ( >19 vs $\leqq$19, $79.4\%$ vs $14.3\%$, p=0.0008), regimen of chemotherapy (CTX vs combined drug, $76.9\%\;vs\;33.3\%$, p=0.04), phase of disease (1st CR vs \geqq2nd$ CR or relapse, $83.3\%\;vs\;30\%$, p=0.01) and method of TBI (fractionated vs single dose, $70.7\%\;vs\;37.5\%$, p=0.05). The influence of French-American-British (FAB) subtypes on relapse rate is not significant, but initial WBC count > 20000/$mm^3$ is associated with increased relapse rate. There is difference in the rate of radiation pneumonitis ($14.3\%\;vs\;25\%$), GVHD ($14.3\%\;vs\;50\%$) and relapse ($21.4\%\;vs\;50\%$) according to fractionated versus single-dose TBI. As mentioned above, fractionated TBI is compatible for the preparative regimen combined with chemotherapy En allogeneic BMT of first CR patients under 41 years of age with suitable donor. Those results from a retrospective, non-randomized study clearly need additional clinical data, ideally from a randomized study.

• Clinical and Experimental Pediatrics
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• v.49 no.11
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• pp.1211-1215
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• 2006

Purpose : In this study, we analyzed the short term changes of thyroid function, incidence and risk factors of thyroid dysfunction soon after allogeneic hematopoietic stem cell transplantation (HSCT) in children. Methods : We enrolled 80 pediatric patients following allogeneic HSCT, at the Catholic HSCT center between January, 2004 and February, 2006. Serum TSH (thyroid stimulating hormone), total serum thyroxine and total serum triiodothyronine levels were systematically measured in 80 patients before the HSCT, and at 1 month, 6 months and 12 months after HSCT. Results : Thyroid function statistically decreased at 1 month after HSCT(P<0.001). Thyroid dysfunction at 1 month was observed in 43 (54 percent) of 80 patients, 31 (39 percent) of whom presented with euthyroid sick syndrome (ETS). Thyroid dysfunction was normalized within 1 year after HSCT. In univariate analysis, malignant disease and the presence of acute graft-versus-host disease (grade ${\geq}II$) were risk factors for ETS (P=0.04, 0.01 respectively). In multivariate analysis, we could not detect an independent risk factor for ETS (P=0.19, 0.06 respectively). Conclusion : The present study suggests that the incidence of thyroid dysfunction is high after allogeneic HSCT. Therefore, regular monitoring of thyroid hormone levels after HSCT is required.