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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.

      • Rapid fecal cytokeratin-19 test and fecal occult blood test in screening for gastrointestinal diseases.

        Kim, Hyunjung,Kim, Yonggoo,Yoon, Sangsoon,Lim, Jihyang,Kim, Myungshin,Lee, Soonwook,Kang, Sunghan,Lee, Eun Jung,Kang, Chang Suk,Han, Kyungja Institute for Clinical Science] 2006 Annals of clinical and laboratory science Vol.36 No.3

        <P>To evaluate the screening power of the fecal cytokeratin-19 test (CK-19) and the fecal occult blood test (FOBT), we performed rapid fecal CK-19 and FOBT tests on 515 stool samples from patients with various GI diseases and 814 stool samples from control patients. The rapid fecal CK-19 test (developed by DiNonA Research Institute, Seoul, Korea) is based on gold immunochromatography and has a sensitivity of 1 ng/ml. The positive rate of the FOBT was 2.1% in controls, 14.0% in GI cancer patients, 3.5% in GI inflammation patients, 11.7% in bone marrow transplant (BMT) patients, and 6.0% in childhood diarrhea patients. Except for the GI inflammation patients, the patients' positive rates for FOBT were all higher than the controls (p <0.05). The positive rate of the fecal CK-19 test was 8.2% in controls, 42.1% in GI cancer patients, 66.0% in GI inflammation patients, 84.8% in BMT patients, and 19.9% in childhood diarrhea patients. In all of the patient groups, positive rates for the CK-19 test were higher than in the controls (p <0.05). The fecal CK-19 test was more frequently positive (42.1%) in GI cancer patients than the FOBT; if both tests were used, the sensitivity was 49.1%. The fecal CK-19 test (but not the FOBT) gave a higher positive rate in GI inflammation patients than the controls, suggesting that the CK-19 test could serve as a screening test for GI inflammation. The highest positive rate of the fecal CK-19 test was found in the BMT group, indicating that significant GI epithelial desquamation had occurred. Although the positive rate of the fecal CK-19 test in childhood diarrhea patients was higher than in the controls, it was much lower than in adults with GI inflammatory disease. Evidently, children with GI inflammation do not desquamate as much intestinal epithelium as adult patients with GI inflammation. This study shows that the rapid fecal GK-19 test, used in conjunction with the FOBT, may be a valuable screening technique for GI diseases and can assist physicians in the differential diagnosis of GI diseases.</P>

      • Antitumor and normal cell protective effect of PKC412 in the athymic mouse model of ovarian cancer.

        Kim, Myungshin,Park, In-Yang,Lim, Jihyang,Kim, Yonggoo,Han, Ku Taek,Chung, Won Heui,Han, Kyungja Institute for Clinical Science] 2006 Annals of clinical and laboratory science Vol.36 No.4

        <P>N-benzoyl-staurosporine (PKC412) is a selective inhibitor of protein kinase C, and it inhibits the growth of human cancer cells. In this study, we examined the antitumor effect of PKC412, given singly and in combination with paclitaxel, on tumor regression and chemotherapeutic side effects by assessing tumor burden and cytokine production responses in vivo. Twenty-six nude mice intraperitoneally inoculated with SKOV3 cells were treated differently in 4 treatment groups: PKC412 plus paclitaxel (n = 7), paclitaxel-only (n = 6), PKC412-only (n = 6), and controls (n = 7). At autopsy, we found that PKC412 itself slightly reduced the mass of tumor but did not fully inhibit tumor formation. The incidence of evident disease was decreased when PKC412 was combined with paclitaxel (43%). From the body weight of the tumor-bearing mice, we observed that PKC412 plus paclitaxel treated mice were less wasted than paclitaxel-only treated mice (18.1 g vs 22.4 g, p = 0.001). We measured intracellular TNFalpha, IFNgamma, IL-4, and IL-10 in stimulated mouse splenocytes using flow cytometry to determine if PKC412 inhibited cytokine production in T cells. TNFalpha, IFNgamma, and IL-10 production were all significantly inhibited in the paclitaxel-treated mice. The inhibitory effects on cytokine production by paclitaxel were compensated with PKC412 combination (p = 0.008, 0.035, 0.014, respectively). From this study, we deduce that PKC412 may have clinical applications in promoting tumor regression in ovarian cancer when combined with paclitaxel. Moreover, PKC412 is able to prevent weight loss and immunosuppression induced by paclitaxel because it rescues normal proliferating cells from cytotoxic effects.</P>

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