• Clinical and Experimental Pediatrics
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• v.53 no.11
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• pp.957-964
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• 2010

Purpose: Our study attempted to determine the prognostic significance of minimal residual disease (MRD) detected by a simplified flow cytometric assay during induction chemotherapy in children with B-cell acute lymphoblastic leukemia (B-ALL). Methods: A total of 98 patients were newly diagnosed with precursor B-ALL from June 2004 to December 2008 at the Asan Medical Center (Seoul, Korea). Of those, 37 were eligible for flow cytometric MRD study analysis on day 14 of their induction treatment. The flow cytometric MRD assay was based on the expression intensity of CD19/CD10/CD34 or aberrant expression of myeloid antigens by bone marrow nucleated cells. Results: Thirty-five patients (94.6%) had CD19-positive leukemic cells that also expressed CD10 and/or CD34, and 18 (48.6%) had leukemic cells with aberrant expression of myeloid antigens. Seven patients with ${\geq}1%$ leukemic cells on day 14 had a significantly lower relapse-free survival (RFS) compared to the 30 patients with lower levels (42.9 % [18.7%] vs. 92.0% [5.4%], $P$=0.004). Stratification into 3 MRD groups (${\geq}1%$, 0.1-1%, and <0.1%) also showed a statistically significant difference in RFS (42.9% [18.7%] vs. 86.9% [8.7%] vs. 100%, $P$=0.013). However, the MRD status had no significant influence on overall survival. Multivariate analysis demonstrated that the MRD level on day 14 was an independent prognostic factor with borderline significance. Conclusion: An MRD assay using simplified flow cytometry during induction chemotherapy may help to identify patients with B-ALL who have an excellent outcome and patients who are at higher risk for relapse.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2219-2225
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• 2015

SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients.

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.97-103
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• 2005

Hypereosinophilic syndrome (HES) is characterized by a sustained eosinophilia of $1,500/mm^3$ or more in the absence of any known causes or the signs and symptoms of organ involvement. We report a 64-year-old man with HES initially presenting with involvement of the liver and bone marrow. Despite controlling the eosinophilia by corticosteroid, he developed a cerebral infarction and later progressive interstitial pneumonia. Brain angiography revealed a severe stenosis of the proximal right internal carotid artery (ICA) and a complete obstruction of the intracranial ICA. An open lung biopsy revealed fibrosis and lymphoplasma cell infiltration without eosinophils, which were consistent with nonspecific interstitial pneumonia.

• BMB Reports
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• v.45 no.12
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• pp.742-747
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• 2012

Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent ($H_2O_2$). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure.

• The Journal of Internal Korean Medicine
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• v.37 no.3
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• pp.539-547
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• 2016

Myelodysplastic syndrome (MDS) is a typical myeloid malignancy characterized by cell dysplasia in bone marrow. Currently, there is no therapeutic treatment for MDS. The only available therapies either relieve symptoms or prevent the development of acute myeloid leukemia (AML). This study aimed to report the effects of traditional Korean medicine (TKM) on MDS by presenting two case reports. The patient in Case 1 was diagnosed with primary MDS and regularly received acupuncture treatments and herbal medicine. In Case 2, a patient with ovarian cancer was diagnosed with secondary MDS, which resulted from an adverse reaction to chemotherapy. This patient took herbal medicine for four years and was hospitalized three times. In order to have their condition evaluated, both patients underwent regular blood tests. The patient in Case 1, who showed blood transfusion dependency, received only two blood transfusions after TKM treatment, and the person’s health condition was stable as of January 2016 without any signs of AML development. The patient in Case 2 also has stable health condition. TKM treatment effectively treated their MDS symptoms and improved their general health conditions without any adverse effects. It also prevented the rapid development of AML and maximized the effects of conservative therapy.

• The Korean Journal of Nuclear Medicine
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• v.10 no.1
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• pp.21-34
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• 1976

The diagnosis of iron deficiency rests upon the correct evaluation of body iron stores. Morphological interpretation of blood film and the red cell indices are not reliable and often absent in mild iron deficiency. Serum iron levels and iron-binding capacity are more sensitive indices of iron deficiency, but they are often normal in iron depletion and mild iron deficiency anemia. They are also subject to many variables which may introduce substantial errors and influenced by many pathologic and physiologic states. Examination of the bone marrow aspirate for stainable iron has been regarded as one of the most sensitive and reliable diagnostic method for detecting iron deficiency, but this also has limitations. Thus, there is still need for a more practical, but sensitive and reliable substitute as a screening test of iron deficiency. Pollack et al. (1965) observed that the intestinal absorption of cobalt was raised in iron-deficient rats and Valberg et al. (1969) found that cobalt absorption was elevated in patients with iron deficiency. A direct correlation was demonstrated between the amounts of radioiron and radiocobalt absorbed. Unlike iron, excess cobalt was excreted by the kidney, the percentage of radioactivity in the urine being directly related to the percentage absorbed from the gastrointestinal tract. Recently a test based on the urinary excretion of an oral dose of $^{57}Co$ has been proposed as a method for detecting iron deficiency. To assess the diagnostic value of urinary cobalt excretion test cobaltous chloride labelled with $1{\mu}Ci\;of\;^{58}Co$ was given by mouth and the percentage of the test dose excreted in the urine was measured by a gamma counter. The mean 24 hour urinary cobalt excretion in control subjects with normal iron stores was 6.1% ($1.9{\sim}15.2%$). Cobalt excretion was markedly increased in patients with iron deficiency and excreted more than 29% of the dose. In contrast, patients with anemia due to causes other than iron deficiency excreted less than 27%. Hence, 24 hour urinary cobalt excretion of 27% or less in a patient with anemia suggets that the primary cause of the anemia is not iron deficiency. A value greater than 27% in an anemic subject suggests that the anemia is caused by iron deficiency. The cobalt excretion test is a simple, sensitive and accurate method for the assessment of body iron stores. It may be particularly valuable in the epidemiological studies of iron deficiency and repeated evaluations of the body iron stores.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.12
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• pp.2021-2030
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• 2020

Objective: Quantitative polymerase chain reaction (qPCR) has been extensively used in the field of mesenchymal stem cell (MSC) research to elucidate their characteristics and clinical potential by normalization of target genes against reference genes (RGs), which are believed to be stably expressed irrespective of various experimental conditions. However, the expression of RGs is also variable depending on the experimental conditions, which may lead to false or contradictory conclusions upon normalization. Due to the current lack of information for a clear list of stable RGs in bovine MSCs, we conducted this study to identify suitable RGs in bovine MSCs. Methods: The cycle threshold values of ten traditionally used RGs (18S ribosomal RNA [18S], beta-2-microglobulin [B2M], H2A histone family, member Z [H2A], peptidylprolyl isomerase A [PPIA], ribosomal protein 4 [RPL4], succinate dehydrogenase complex, subunit A [SDHA], beta actin [ACTB], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], TATA box binding protein [TBP], and hypoxanthine phosphoribosyltrasnfrase1 [HPRT1]) in bovine bone marrow-derived MSCs (bBMMSCs) were validated for their stabilities using three types of RG evaluation algorithms (geNorm, Normfinder, and Bestkeeper). The effect of validated RGs was then verified by normalization of lineage-specific genes (fatty acid binding protein 4 [FABP4] and osteonectin [ON]) expressions during differentiations of bBMMSCs or POU class 5 homeobox 1 (OCT4) expression between bBMMSCs and dermal skins. Results: Based on the results obtained for the three most stable RGs from geNorm (TBP, RPL4, and H2A), Normfinder (TBP, RPL4, and SDHA), and Bestkeeper (TBP, RPL4, and SDHA), it was comprehensively determined that TBP and RPL4 were the most stable RGs in bBMMSCs. However, traditional RGs were suggested to be the least stable (18S) or moderately stable (GAPDH and ACTB) in bBMMSCs. Normalization of FABP4 or ON against TBP, RPL4, and 18S presented significant differences during differentiation of bBMMSCs. However, although significantly low expression of OCT4 was detected in dermal skins compared to that in bBMMSCs when TBP and RPL4 were used in normalization, normalization against 18S exhibited no significance. Conclusion: This study proposes that TBP and RPL4 were suitable as stable RGs for qPCR study in bovine MSCs.

• Applied Microscopy
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• v.33 no.1
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• pp.41-48
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• 2003

The hemopoiesis in human fetal spleen was studied with transmission electron microscope. There were undifferentiated proerythroblast, basophilic erythroblast, polychromatophilic erythroblast, and acidophilic erythroblast. Besides, enucleated nuclei and mitoses were present. Groups of erythroblastic cells were surrounded by certain cell. The structure was identical to erythropoietic island found in fetal liver. So, erythropoisis in spleen was developing in a pattern similar to fetal liver. Megakaryobalst were found in spleen, but there was no mature cells, cells in mitosis nor platelet formation. It was not clear whether megakaryoblast in circulation was trapped in spleen or participated in megakaryopoiesis. In summary, erythropoiesis took place in fetal spleen in a pattern similar to fetal liver and bone marrow. But it was not certain whether megakaryopoiesis took place in fetal spleen.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.118-122
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• 1993

To evaluate the genotoxic effect of $^{131}I$, lymphocytes from 9 patients who underwent large dose (150 mCi) $^{131}I$ therapy after total thyroidectomy were studied for sister chromatid exchanges (SCE) before and after their first radioiodine treatments. Frequency of SCE (FSCE) was counted in chromosomes of 30 lymphocytes in each patients, and was expressed as numbers of SCE per cell. Numbers of leukocytes were also observed during $^{131}I$ therapy. Pretreatment FSCE ($4.2{\pm}0.7$) was not different from the control ($3.8{\pm}0.4$, p=0.17). However, the frequency was significantly elevated after $^{131}I$ administration (at the second day, $7.9{\pm}0.8$, p<0.001) and was diminished but still significantly elevated after a week (at 9th day, $6.4{\pm}0.6$, p<0.001). While counts of leukocytes in the peripheral blood showed no change (p> 0.05). In conclusion, chromatids of human lymphocytes were significantly damaged after $^{131}I$ treatment without any bone marrow supression. And the repair of SCE was not complete within one week.

• Food Science and Preservation
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• v.24 no.8
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• pp.1122-1128
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• 2017

Pumpkin has long been used as traditional health materials in oriental medicine, pharmacy, medicine, and food industries in many countries. In this study, the water extract and two active components from tendril of young C. moschata Duch. were investigated on inflammation inhibitory activity. The water extract of young C. moschata Duch. showed high cell viability over 95% and it decreased the production of interlukin 6 (IL-6) and tumor necrosis factor (TNF-${\alpha}$) in the capacity of mouse bone marrow-derived macrophages (BMDM) upon lipopolysaccharide (LPS) stimulation. Also, isolated fraction (B4) suppressed the secretion of IL-6 and TNF-${\alpha}$. Among the domestically cultivated pumpkins, B4 fraction contained in the tendril part of them and it comprised of the order of tendril from Cucurbita pepo var. cylindrica, old of C. moschata Duch., and young of C. moschata Duch. These results suggest that water extracts of C. moschata Duch. and purified active compound, rutin, show anti-inflammation activity by suppression of the secretion of IL-6 and TNF-${\alpha}$. It can be applicable as pharmaceutical materials.