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        Vitamin B<sub>12</sub>-Responsive Pancytopenia Mimicking Myelodysplastic Syndrome

        Kim, Myungshin,Lee, Sung-Eun,Park, Joonhong,Lim, Jihyang,Cho, Byung-Sik,Kim, Yoo-Jin,Kim, Hee-Je,Lee, Seok,Min, Chang-Ki,Kim, Yonggoo,Cho, Seok-Goo S. Karger AG 2011 Acta haematologica Vol.125 No.4

        <P>This study presents 12 patients (7 women and 5 men) with vitamin B(12)-responsive pancytopenia who had discordant laboratory findings and were misdiagnosed as having myelodysplastic syndrome (MDS). The median hemoglobin level was 6.5 g/dl, and the leukocyte and platelet counts were 2.85 × 10(9)/l and 55.5 × 10(9)/l, respectively. The median serum lactate dehydrogenase level was high (3,204.5 IU/l). The serum vitamin B(12) levels were within normal limits at the initial evaluation, but a serial follow-up of the vitamin B(12) levels revealed either fluctuations or a gradual decrease. The patients were initially diagnosed with MDS and responded rapidly to a 7-day parenteral B(12) treatment with normal complete blood counts (CBCs). We propose that patients suspected to have MDS may suffer from vitamin B(12) deficiency and that this can be revealed by a normalization of CBCs following 7 days of treatment with parental vitamin B(12).</P>

      • OB-40 : Isolation and Characterization of Chorionic Mesenchymal Stromal Cells from Human Full Term Placenta

        ( Hye Jung Yun ),( Ju Young Cheon ),( Narinay Kim ),( In Yang Park ),( Bo Kyung Koo ),( Jiyeon Kim ),( Ji Hyun Kim ),( Ahlm Kwon,),( Myungshin Kim ),( Yonggoo Kim ),( Jong Chul Shin ),( Jong Hoon Kim 대한산부인과학회 2014 대한산부인과학회 학술대회 Vol.100 No.-

        목적: Adult stem cells are considered as an excellent source for research because they pose few ethical problems and limitations in terms of availability. Although many types of stem cells are available, the sources of the stem cells selected for clinical use should possess the ability to renew, be easily isolated and be pluripotent. These properties can be satisfied with human term placental-derived stromal cells. It is essential to understand the expansion capability and potency of isolated stem cells. 방법: This study focused on the characterization of mesenchymal stromal cells (MSCs) from the chorion of human full term placenta from 15 donors.We characterized the surface markers and multilineage differentiation (adipogenic, osteogenic and chondrogenic induction) ability of cultured chorionic MSCs. We also present our findings regarding their growth rate and gene expressions. 결과: Chorionic MSCs revealed homologous fibroblast-like morphology and expressed CD73, CD29, CD105, and CD90. The hematopoietic stem cell markers including HLA DR, CD11b, CD34, CD79a, and CD45 were not expressed. The growth kinetics of their serial passage was steady at the later passages (passage 10). The multilineage capability of chorionic MSCs was demonstrated by successful adipogenic, osteogenic and chondrogenic differentiation and associated gene expression. Chorionic MSCs expressed genes associated with undifferentiated cells (NANOG, OCT4, REX1) and cardiogenic or neurogenic markers such as SOX2, FGF4, NES, MAP2, and NF. TERT was negative in all the samples. 결론: A low HLA DR expression suggests that chorionic MSCs may serve as a great source of stem cells for transplantation because of their immune- privileged status and their immunosuppressive effect. Based on these unique properties, it is concluded that chorionic MSCs are pluripotent stem cells that are probably less differentiated than BM-MSCs, and they have considerable potential for use in cell-based therapies.

      • 한국인의 급성 림프구성 백혈병과 HLA 연관성

        이은정,윤정숙,김명신,임지향,김용구,한경자,김학기,민우성,김춘추,김원일 대한조혈모세포이식학회 2000 대한조혈모세포이식학회지 Vol.5 No.2

        배경:주조직 적합항원 복합체(Major Histocompatibility Complex : MHC)는 쥐에서 처음 이식 항원으로 발견된 이래 이식 면역 분야에서 광범위하게 연구되어 왔으며, 면역 반응을 조절하는 주요 유전자로서 감염, 종양, 자가면역 질환 등의 발생에 관여한다. 사람에서 자가 면역 질환과 HLA 연관성이 증명되어 있으나, 백혈병에서 HLA 연관성에 관한 연구는 드물며 대상군 수가 유의한 결론을 얻기에 부족하다. 본 연구에서는 급성 림프구성 백혈병(ALL) 환자를 대상으로 HLA class I, II 항원 및 2-유전자좌 일배체형 빈도를 구하고, 이를 정상 대조군과 비교하는 통계적 방법으로 ALL군과 연관된 HLA 항원 및 일배체형이 있는지 살펴보고, ALL군은 FAB 분류와 면역 표현형 분류에 따른 아군으로 분류하여 각 아군과 연관된 HLA 항원 및 일배체형을 관찰함으로써 ALL 군과 HLA의 연관성을 규명해 보고자 하였다. 방법:1991년 1월부터 1998년 7월까지 성모병원에 내원하여 미세림프구독성검사를 이용한 혈청학적 방법으로 HLA Class I, II 항원 형별 검사를 실시한 222례의 ALL 환자를 대상으로 하여 FAB 분류 및 면역 표현형 아군에서 HLA 항원 빈도와 유전자 빈도를 구하고, 항원 빈도를 대조군과 비교하여 Haldane‘s 법에 따라 상대 위험도를 구하고 chi-square method로 유의성을 검정하였다. ALL 각 질환군과 아군에서 square root 법을 이용하여 HLA A-B, C-B, B-DR 2-유전자좌 일배체형 빈도를 구하고, 이를 대조군과 비교하여 chi-square 법으로 유의성을 검정하였다. 결과:1) Cw8이 ALL군에서 RR 0.12로 매우 감소하여 강한 연관성 정도를 나타냈고, p-value 0.001 이하의 높은 통계적 유의성을 나타냈다. 이는 Cw8이 ALL 발생에 저항성을 나타내는 유전자이거나, 저항성을 나타내는 다른 유전자에 linkage되어있을 가능성을 시사하며, 또는 Cw8이 leukemia virus 등 외부 항원에 대해 증가된 면역 반응을 암호화하는 유전자이거나, 면역 반응을 조절하는 다른 유전자에 linkage되어있을 가능성이나, Cw8이 면역 감시 기능에 주요 역할을 담당하는 항원일 가능성을 시사한다. 2) Cw3이 ALL군에서 유의하게 증가하였고 p-value 0.001 이하의 통계적 유의성을 나타내어, Cw3이 급성 림프구성 백혈병 발생을 예측하는 표지자가 될 수 있을 것으로 사료되었다. 3) B-blank와 DR-blank 유전자 빈도가 ALL 군에서 증가하였으며, 특히 이 현상은 DR locus에서 현저하으며 이는 ALL 질환군에서 B와 DR 항원의 동형접합체의 증가 때문이거나, 대립유전자의 변형이나 소실로 인하여 검출되지 않은 항원이 증가한 때문으로 사료된다. 4) FAB 분류 및 면역 표현형, 임상적 아군과 연관된 HLA 항원들이 검출되었으며, 특히 A11, B62, DR4는 T-cell 면역 표면형과 높은 연관성을 나타냈고, 이중 DR4는 CD3과 100%의 일치율을 보여 DR4가 T-cell ALL 발생을 예측하는 강력한 표지자가 될 수 있을 것으로 사료되었다. 결론:급성 림프구성 백혈병은 HLA와 연관된 질환이며, 급성 림프구성 백혈병의 발생 및 백혈병 세포의 분화 단계를 예측하는데 본 연구가 유용한 기준 자료가 될 것으로 생각되었다. Backgrounds:The MHC(Major Histocompatibility Complex) has been widely studied in the field of transplantation immunology, since initially defined as transplantation antigen in mouse in 1936, and it's a major genetic complex which regulates immune responses, associated with development of infectious diseases, cancers, or autoimmune diseases. Although associations have been demonstrated between many autoimmune diseases and HLA antigens or haplotypes in human, the studies of human leukemia or other hemopoietic disease and HLA association are rare and have too small sample sizes to get a significant result. We tried to investigate the association of ALL with HLA in 222 patients by using appropriate statistical methods, and invesgate HLA associations in FAB and immunological subgroup in ALL. Methods: The subject of this study was 222 patients with ALL who admitted in St. Mary's hospital from January 1991 to July 1998 and was typed for HLA Class I, II antigens by using serological method of NIH standard microlymphocytotoxicity. We calculated the HLA antigen, gene and 2-locus haplotype frequencies in each ALL subgroup including FAB classification and immunophenotypical subgroup, and calculated relative risk by Haldane's method by comparing HLA antigen frequencies in ALL group with those in normal control population. The chi-square method or Fisher's exact test was used to assess the significance of the differencies in the antigen and haplogtype distributions in the control vs. ALL population. Results: 1)The frequencies of Cw8 were decreased in ALL with relative risk 0.12 and high statistical significance with p-values less than 0.001 was found, suggesting strong Cw8 associations with ALL. This means Cw8 may be a gene which resists to development of ALL or may be linked to other recessive gene, or Cw8 may be a gene which encodes increased immune responses to exogenous antigens such as leukemia virus, or may be linked to other gene. Otherwise, Cw8 may be an antigen which has a key role in immune surveillance to development of ALL. 2) The frequencies of Cw3 were increased significantly in ALL and revealed p-values less than 0.001 in ALL, suggesting Cw3 could be a marker predicting development of ALL. 3) B and DR-blank gene frequencies were increased in ALL and this phenomenon was prominent in DR locus, showing 12.9% of DR-blank gene frequencies and 45.80 of relative risk in overall 630 patients who were typed for DR antigen. This suggests increased B and DR homozygosity or increased undetected antigens due to loss or modification of DR allele in ALL. 4) Several HLA antigens were detected associated with each ALL group and subgroup. Especially A11, B62, DR4 antigens were strongly associated with T-cell immunophenotypes, and DR4 had a 100% correlation with CD3, suggesting DR4 could be a strong marker predicting development of T-cell ALL. Conclusion: ALL is a disease associated with HLA and this study will be worth predicting development of ALL, and differentiation stages of leukemic cells in ALL.

      • Donor-Specific HLA Class I and CREG Antibodies in Complement-Dependent Cytotoxicity-Negative Renal Transplants.

        Kim, Yonggoo,Yang, Chul Woo,Moon, In-Sung,Kim, Myungshin,Lim, Jihyang,Park, Yeon-Joon,Han, Kyungja,Oh, Eun-Jee Institute for Clinical Science] 2010 Annals of clinical and laboratory science Vol.40 No.4

        <P>Development of a solid-phase, single antigen panel reactive antibody test (SA-PRA) permits the analysis of antibody specificities. This study determined the impact of donor-specific antibodies (DSA) against class I HLA private antigens (DS-HLA) or HLA-A and -B cross-reactive group (DS-CREG) in kidney transplantation. Pre- and post-transplant sera of 133 renal allograft patients who had negative pretransplant complement-dependent cytotoxicity were tested for HLA class I antibody specificities by SA-PRA. Clinical relevance of the flow cytometric crossmatch test (FCXM) for the detection of class I DS-HLA or DS-CREG was analyzed. The sensitivity of FCXM to detect SA-PRA-defined class I DSA was 50% (5/10) and the specificity was 98.4% (121/123). Of 133 renal allograft recipients, including 26 patients with biopsy-proven acute antibody-mediated rejection (AMR), pretransplant DS-HLA or DS-CREG were detected in 10 patients. Pretransplant DSA were associated with AMR (p = 0.012) and a low calculated glomerular filtration rate (p = 0.036). In the analysis of post-transplant sera, the presence of either type of HLA antibodies and the de novo development of DSA were correlated with AMR (p <0.001). This study demonstrates that detection of DSA, including DS-HLA and DS-CREG, using the SA-PRA assay is useful to identify the renal allograft recipients with poor transplant outcome.</P>

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        Potential Risk Factors Associated With Vascular Diseases in Patients Receiving Treatment for Hypertension

        Kim, Hyunjung,Park, Joonhong,Chae, Hyojin,Lee, Gun Dong,Lee, Sang Yoon,Lee, Jong Min,Oh, Yong-Seog,Kim, Myungshin,Kim, Yonggoo The Korean Society for Laboratory Medicine 2016 Annals of Laboratory Medicine Vol.36 No.3

        <P><B>Background</B></P><P>Currently, the hypertension (HTN) patients undergo appropriate medical treatment, and traditional risk factors are highly controlled. Therefore, potential risk factors of atherosclerotic vascular diseases (AVD) and venous thromboembolisms (VTE) in HTN should be reconsidered. We investigated thrombophilic genetic mutations and existing biomarkers for AVD or VTE in HTN patients receiving treatment.</P><P><B>Methods</B></P><P>A total of 183 patients were enrolled: AVD with HTN (group A, n=45), VTE with HTN (group B, n=62), and HTN patients without any vascular diseases (group C, n=76). The lipid profile, homocysteine (Hcy) levels, D-dimers, fibrinogen, antithrombin, lupus anticoagulant, and anti-cardiolipin antibody (aCL) were evaluated. <I>Prothrombin</I> G20210A, <I>Factor V</I> G1691A, and <I>methylenetetrahydrofolate reductase (MTHFR)</I> C677T and A1298C were analyzed.</P><P><B>Results</B></P><P>All patients revealed wild type <I>prothrombin</I> G20210A and <I>Factor V</I> G1691A polymorphisms. The frequency of <I>MTHFR</I> polymorphisms was 677CT (n=84, 45.9%); 677TT (n=46, 25.1%); 1298AC (n=46, 25.1%); and 1298CC (n=2, 1.1%). The <I>MTHFR</I> 677TT genotype tended to increase the odds ratio (OR) to AVD events in HTN patients (OR 2.648, confidence interval 0.982-7.143, <I>P</I>=0.05). The group A demonstrated significantly higher Hcy levels (<I>P</I>=0.009), fibrinogen (<I>P</I>=0.004), and platelet counts (<I>P</I>=0.04) than group C. Group B had significantly higher levels of D-dimers (<I>P</I>=0.0001), platelet count (<I>P</I>=0.0002), and aCL (<I>P</I>=0.02) frequency than group C.</P><P><B>Conclusions</B></P><P>The <I>MTHFR</I> 677TT genotype and Hcy level could be potential risk factors associated with development of AVD in HTN patients receiving treatment. D-dimer and aCL might be useful to estimate the occurrence of VTE in them.</P>

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