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Biomedical subjects

Hyun Sook Chi

Publications and source records attributed to Hyun Sook Chi.

18 recordsLinked to original sources

Identification of 13q deletion, trisomy 1q, and IgH rearrangement as the most frequent chromosomal changes found in Korean patients with multiple myeloma.

The most frequent genetic aberrations in multiple myeloma (MM) are 13q deletions and translocations involving the immunoglobulin heavy chain gene (IGH). There have been no reports on the cytogenetic abnormalities found in Korean patients with MM. We investigated the actual prevalence and prognostic value of cytogenetic changes using fluorescence in situ hybridization (FISH). FISH studies with 12 different specific probes for the regions containing the genes or chromosome regions (13q, 1q, IGH, p53, MLL, p16, CEP 7, CEP 11, and CEP 12) were performed in 128 patients. The most frequent change found was 13q deletion (48%), followed by trisomy 1q (45%), IGH translocation (37%), and trisomy 11 (26%). Among the three different probes used to detect 13q deletion, D13S25 (48/58) was the most sensitive probe compared to RB (43/58) and D13S319 (39/58). Among the patients showing one or more changes by FISH, 75% (82/110) had a 13q deletion, a trisomy 1q, or an IGH translocation. Azotemia, anemia, thrombocytopenia, intramedullary plasmacytosis, and stage were significantly associated with the 13q deletion; serum beta(2)-microglobulin, thrombocytopenia, and intramedullary plasmacytosis were also related to trisomy 1q. The pattern of molecular cytogenetic changes in Korean patients with MM is somewhat different from what has been observed in reported Caucasian populations: 37 versus 50-70% with regard to the IGH translocation. The prevalence of the 13q deletion was similar in Korean and Caucasian populations, 48 versus 30-50%. We suggest that the detection of at least these three genetic changes, 13q- trisomy 1q, and an IGH rearrangement, would be helpful for follow-up of Korean patients with MM.

Adult↗

Recommendation of the use of myeloblast percentage among non-erythroid cells instead of percentage among total nucleated cells for therapeutic response assessment in acute erythroid leukemia.

The diagnostic criteria of acute erythroid leukemias (AEL) has been revised by WHO in 2001. The National Cancer Institute (NCI) published a set of standardized diagnostic and response criteria for acute myeloid leukemia in 1990, which was revised in 2003. The aim of the present study was to establish the best criteria for therapeutic response assessment in the newly classified AEL and evaluate patient outcomes. Fifty-two patients with AEL as defined by the new WHO criteria were evaluated in this study. The following seven indices for therapeutic response assessment were evaluated: (i) NCI criteria (myeloblast percentage among total nucleated cells (TNC) and cellularity); (ii) myeloblast percentage among non-erythroid cells (NEC) and cellularity; (iii) erythroid series percentage among TNC; (iv) pronormoblast percentage among erythroid cells; (v) ratio of pronormoblasts and blasts; (vi) maturation arrest index; and (vii) disappearance of erythroid dysplasia. Complete remission (CR) patients with <5% of myeloblast/NEC (NEC-CR) showed significantly longer overall survival periods (mean 55.8 months) compared to CR patients with >5% myeloblast/NEC (mean 11.7 months, P = 0.006). NEC-CR patients also had longer event-free survival (median 16.4 months) compared to patients with >5% and <20% of myeloblast/NEC (median 6.2 months) (P = 0.044). The other indices for therapeutic response assessment are not significant for predictability of relapse and outcomes. Therefore, we recommend that the myeloblast percentage among NEC be used instead of myeloblast percentage among TNC for therapeutic response assessment in AEL.

Adolescent↗

Inferior prognostic outcome in acute promyelocytic leukemia with alterations of FLT3 gene.

Alterations of the FLT3 gene, in the form of internal tandem duplications (ITD) and D835 point mutations, occur frequently in acute promyelocytic leukemia (APL). We therefore evaluated the frequency and clinical relevance of FLT3 aberrations in a series of Korean APL patients. We assayed FLT3 ITD and D835 mutation status in 75 newly diagnosed APL patients and we correlated the presence of these mutations with clinical parameters and outcomes. Of the 75 patients, fifteen (20.0%) carried FLT3 mutations, nine (12.0%) with FLT3 ITD, seven (9.3%) with D835 mutations and one with both types. Patients presenting with higher leukocyte counts (>10 x 10(9)/L) had a significantly higher frequency of FLT3 ITD (P = 0.030). There was no association between FLT3 aberrations and other clinicohematologic features including age, gender, M3 variant morphology and PML/RARalpha subtype. Death at presentation before induction chemotherapy was significantly more frequent in patients with ITD than in those without ITD (33.3% vs. 4.5%, P = 0.020), but was not significantly related to the presence of D835 mutations (28.6% vs. 5.9%, P = 0.094). Both ITD and D835 mutations were associated with shortened event-free survival (P = 0.048 and P = 0.029, respectively), but there was no correlation between disease-free survival among the 61 patients who achieved complete remission and the presence of FLT3 mutations (P = 0.543 for ITD and P = 0.277 for D835). FLT3 mutations were less frequent in Korean APL patients than in Western APL patients. In Korean patients, however, FLT3 mutations were associated with higher leukemic burdens and early deaths before remission resulting in inferior prognosis.

Adolescent↗

Prognostic significance of multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression in acute leukemia.

The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.

Adolescent↗

Gene--nutrition interactions in coronary artery disease: correlation between the MTHFR C677T polymorphism and folate and homocysteine status in a Korean population.

INTRODUCTION: Elevated plasma total homocysteine is a major risk for coronary artery disease (CAD). Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine metabolism; a common C677T mutation in the MTHFR gene results in decreased enzyme activity, and contributes to increased homocysteine levels and decreased folate levels. We investigated the frequency of MTHFR C677T alleles in a Korean population, determined the genotype-specific threshold levels of folate or vitamin B12, and investigated the relationship between the TT genotype and the risk of CAD. MATERIALS AND METHODS: We enrolled a study population of 163 CAD patients and 50 control subjects, and screened the MTHFR C677T polymorphism using real-time PCR with melting point analysis. Levels of plasma homocysteine, folate and vitamin B12 were also determined. We then defined the genotype-specific threshold values of folate and vitamin B12 required to keep homocysteine levels in a normal range for individuals of each MTHFR C677T genotype. RESULTS: The frequency of the TT genotype was 18% in control subjects and 26% in patients group (P>0.05). Individuals homozygous for the TT genotype had significantly elevated homocysteine levels (P<0.05). The genotype-specific folate threshold level was significantly higher in TT individuals than in the CC or CT genotypes. The OR of individuals with low folate status and the TT genotype to estimate the relative risk of CAD was 2.2 and the OR of those with high folate status and the TT genotype was 1.5 (95% CI, 0.5-9.6 and 0.7-3.2, respectively). CONCLUSION: We were able to define a gene-nutrient interaction that shows a higher risk for CAD based on specific threshold folate levels required by different MTHFR C677T genotypes in a Korean population.

Adult↗

Effects of Ginkgo biloba on haemostatic factors and inflammation in chronic peritoneal dialysis patients.

Ginkgo biloba extract decreased plasma D-dimer concentration, a marker of intravascular coagulation, in chronic peritoneal dialysis patients. Blood levels of fibrinogen, von Willebrand factor, hs-CRP, albumin and liver enzyme levels were not significantly changed. No bleeding episode was reported. These results suggest that Ginkgo biloba extract was effective in partially reversing the thrombogenic coagulation profile without increasing the risk of bleeding.

Anti-Inflammatory Agents↗

Systemic inflammatory syndrome and hepatic inflammatory cell infiltration caused by an interleukin-6 producing pheochromocytoma.

Pheochromocytoma is a tumor that produces a variety of biologically active substances in addition to catecholamines. We report here a patient with a pheochromocytoma, who presented with acute inflammatory symptoms and marked abnormalities in liver function and hematological tests. A 31-year-old man, who had experienced intermittent fever, chills and weight loss during the previous several months, was referred to our hospital for further evaluation. Laboratory examination revealed anemia, leukocytosis with elevated inflammatory markers, and abnormalities in coagulation and liver function tests. Histological examination revealed a marked plasmacytosis in the bone marrow and lymphocyte infiltration into the portal area of the liver. Along with increases in serum catecholamine and urine catecholamine metabolites, his serum interleukin (IL)-6 level was increased to 300 pg/ml, compared with a normal range of 3-12 pg/ml. Left adrenalectomy was performed. The adrenal tumor was densely immunostained with antibody to IL-6. After resection of his adrenal tumor, his serum IL-6 level returned to normal (11 pg/ml) and all symptoms subsided with normalization of laboratory findings.

Acute Disease↗

Quantification of AML1-ETO fusion transcript as a prognostic indicator in acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: In spite of the high complete remission rate that chemotherapy achieves in acute myeloid leukemia with AML1-ETO gene rearrangement, relapse is a major cause of treatment failure in this condition. We aimed to determine a predictor of relapse with the real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) of AML1-ETO chimeric mRNA. DESIGN AND METHODS: We serially monitored AML1-ETO fusion transcripts using RQ-PCR in 113 bone marrow or peripheral blood samples from 21 patients with AML1-ETO-positive acute myeloid leukemia and analyzed the prognostic relevance of the results. RESULTS: Higher transcript levels at diagnosis were associated with a higher probability of relapse (p=0.038 in all patients and p=0.001 in adult patients). A decrease of less than 3-log at the time of achieving complete remission was also associated with a higher risk of relapse (p=0.035 in all patients and p=0.011 in adult patients). RQ-PCR detected the reappearance of AML1-ETO fusion transcripts in both peripheral blood and bone marrow during apparent complete remission. Detection of the transcripts preceded hematologic relapse by one to three months. The transcript levels in peripheral blood correlated with those in bone marrow at the same time point. INTERPRETATION AND CONCLUSIONS: Our findings indicate that regular monitoring of AML1-ETO chimeric transcript levels by RQ-PCR on bone marrow or peripheral blood samples could be extremely useful for the selection of high-risk patients and be an early predictor of relapse.

Adolescent↗

Effects of celecoxib on high-sensitivity C-reactive protein in chronic peritoneal dialysis patients.

To evaluate the effects of celecoxib, a cyclooxygenase-2 inhibitor, on the level of high-sensitivity C-reactive protein (hs-CRP), D-dimer, von Willebrand factor (vWF) and troponin-T, 46 chronic peritoneal dialysis (CPD) patients with hs-CRP equal or greater than 0.25 mg/dL were randomized to the treatment group who took 200 mg of celecoxib daily for 4 weeks or to the control group who did not take the medication. The levels of hs-CRP, albumin, D-dimer, vWF and troponin-T were measured at baseline and at 4 weeks of the study. Baseline values of all the parameters were not significantly different between the two groups. In the control group, the levels of hs-CRP, albumin, D-dimer, vWF and troponin-T did not change. In the treatment group, administration of celecoxib for 4 weeks significantly reduced hs-CRP from median 0.77 (range 0.25-7.08) to 0.39 mg/dL (range 0.11-5.22, p<0.05). The levels of albumin, D-dimer, vWF and troponin-T levels were not affected by the administration of celecoxib. These results showed that celecoxib had an antiinflammatory effect in usual dosage in CPD patients.

Adult↗

Polymerase chain reaction-based diagnosis of bone marrow involvement in 170 cases of non-Hodgkin lymphoma.

BACKGROUND: Up to the current time, diagnosis of bone marrow (BM) involvement in non-Hodgkin lymphoma (NHL) has been based on morphologic findings. Polymerase chain reaction (PCR) for antigen receptor gene rearrangements has the potential to increase the detection sensitivity of minimal degrees of BM involvement. The authors therefore assessed PCR-based clonalities of BM concurrently with morphology from 170 cases with NHL and evaluated the usefulness of comparative analysis of clonalities between bilateral BMs and the lymph node and the clinical significance of PCR based clonalities of BM. METHODS: Bilateral BM clot sections of 170 cases and 47 lymph nodes were tested for immunoglobulin heavy chain gene rearrangement or T-cell receptor gamma gene rearrangement according to the B- or T-lineage of the lymph node. RESULTS: When compared with morphology, the results of PCR showed an unexpectedly low positive concordance rate of 61.0% for B-cell NHL and 57.1% for T-cell NHL. When the clonality of BM was compared with that of lymph nodes in B-cell NHL, bilateral clonalities of BM showed high concordance with the clonality of the lymph nodes. PCR-based clonality did not show significant impact on survival. CONCLUSIONS: Morphology remains the gold standard in the evaluation of BM involvement by NHL. Although the comparative analysis of BM clonality and that of the lymph nodes is considered a valuable tool that increases the reliability of clonality, PCR-based clonality of BM does not significantly add to the sensitivity of diagnosing BM involvement by NHL.

Adolescent↗

Predominance of trisomy 1q in myelodysplastic syndromes in Korea: is there an ethnic difference? A 3-year multi-center study.

A predominance of total or partial chromosomal losses and the rarity of translocations are characteristics of myelodysplastic syndrome (MDS), and 5q,-5, -7 and +8 are known to be the most predominant chromosomal changes. To investigate whether the incidence and the pattern of chromosomal changes in MDS varies by location in Korea, we reviewed the cytogenetic results of 205 MDS cases from three medical centers. Distribution of MDS subtypes and the incidence of chromosomal aberration (44.8%) of MDS in Korea were similar to those found in other countries, however, their patterns were different. Translocations (40.4%) predominated over partial or total deletions (36.3%) in Korea. The most common abnormalities in MDS were trisomy 8, trisomy 1q, -5/5q-, and -7/7q-, which occurred in 18(19.5%), 14(15.2%), 12(13.0%), and 11(11.9%) patients, respectively. It is of note that trisomy 1q, which is rarely reported in hematologic malignancies, was the second most common change associated with MDS in Korea, and that structural anomalies of chromosomes 1(19.6%) exceeded that of chromosome 5(15.2%). The most common sole anomalies were trisomy 8(7.6%) and 14(78%) of 18 cases with chromosome 1 anomalies accompanied by other chromosomal abnormalities, suggesting that the changes of chromosome 1 may be evolutionary events rather than sporadic events. In conclusion, trisomy 1q and trisomy 8 predominate in Korean MDS, suggesting the likelihood of ethnic differences.

Chromosomes, Human, Pair 1↗

Comparison of microvessel density before and after peripheral blood stem cell transplantation in multiple myeloma patients and its clinical implications: multicenter trial.

Bone marrow angiogenesis has been reported to increase in several hematologic malignant diseases, including multiple myeloma. Because high-dose chemotherapy combined with autologous stem cell transplantation (SCT) improves the response rate, event-free survival, and overall survival in patients with multiple myeloma (MM), we studied the changes in bone marrow microvessel density (MVD) in 21 patients who underwent high-dose chemotherapy combined with autologous SCT to determine whether there was persistently increased angiogenesis at the time of response. Bone marrow biopsy specimens were obtained before and after SCT for each patient and immunostained with anti-CD34 antibodies for the identification of microvascular endothelial cells. The mean value of MVD in 21 MM patients at initial diagnosis was 46.0 +/- 24.0 and in healthy controls was 26.8 +/- 8.54 (P = .046). The mean MVD at initial diagnosis was 46.0 +/- 24.0 compared with 29.0 +/- 12.5 after achievement of response with SCT, and there was a statistically significant difference (P = .004). Sixteen of 21 patients (76.2%) had decreased MVD after SCT, and 5 patients were found to have a greater than 50% decrease in MVD after SCT. However, there was no difference in overall survival between the patient group with decreased MVD after SCT and that without decreased MVD (P = .9370). These results suggest that angiogenesis plays an important role in MM. In addition, the persistence of MVD at the time of response indicates continuous stimulus of microvessels by minimal residual disease even after SCT.

Adult↗

Adequately washed bronchoscope does not induce false-positive amplification tests on bronchial aspirates in the diagnosis of pulmonary tuberculosis.

STUDY OBJECTIVES: To investigate the clinical usefulness of amplification (COBAS AMPLICOR; Roche Diagnostics Systems; Branchburg, NJ) on bronchoscopic aspirate specimens in the diagnosis of pulmonary tuberculosis, with particular regard to the possibility of false-positive results in subsequent specimens due to residual Mycobacterium tuberculosis DNA. DESIGN AND SETTING: A prospective clinical study at a tertiary referral medical center. PARTICIPANTS AND METHODS: Four hundred fiberoptic bronchoscopic procedures were performed, using seven bronchoscopes on 335 consecutive patients, for therapeutic or diagnostic purposes. Serial bronchial aspirates were collected and tested for M tuberculosis, using COBAS AMPLICOR (CA). Bronchoscopes were cleaned and disinfected automatically, between patient use, by the same endoscope washer. The name of each bronchoscope and the sequence of its use were recorded, together with the sequence of washing. The CA results were compared with the bacteriologic and histologic results for M tuberculosis infection. When there was a suspicion of contamination, outward polymerase chain reaction analysis was performed. RESULTS: Of 392 specimens (332 subjects), excluding the 8 specimens (4 subjects) in which bacteriologic and histologic analyses were omitted, a smear-positive result for acid-fast bacilli (AFB), culture-positive or biopsy-positive results, and CA-positive results were obtained in 16, 49, and 32 specimens, respectively. In AFB smear-positive subjects, the sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were 92%, 67%, 92%, and 67%, respectively. In AFB smear-negative subjects, the sensitivity, specificity, PPV, and NPV values were 38%, 99%, 74%, and 94%, respectively. The CA test was more sensitive than the AFB smears for the diagnosis of pulmonary tuberculosis (53% vs 27%, respectively; p < 0.05). False-positive CA results were seen in only six specimens. Three of these six subjects received a diagnosis of pulmonary tuberculosis on clinical and radiologic grounds, and none of the six results seemed to be associated with bronchoscopic cross-contamination. CONCLUSIONS: Adequately cleaned and disinfected bronchoscopes did not cause false-positive amplification test results for M tuberculosis on bronchial aspirates by cross-contamination. Furthermore, sensitivity was greater with the CA tests. Therefore, CA tests on bronchial aspirates seem to be useful in the diagnosis of pulmonary tuberculosis.

Adult↗

Frequencies of C282Y and H63D mutations and transferrin saturation indices in the Korean population.

Hereditary hemochromatosis (HHC) is an autosomal recessive disorder that damages various organs because of the deposition of excess iron. At the human hemochromatosis (HFE) gene, two mutations of C282Y and H63D have been reported. The frequencies of C282Y and H63D mutations vary among ethnic groups. At present, the most suitable screening test for HHC is the assessment of transferrin saturation (TS). We investigated the distribution of TS and the frequencies of C282Y and H63D mutations among Koreans. TS was measured in 2152 subjects who visited the health promotion center for a checkup. The mean (+/-SD) of TS was 41.7+/-15.4%. We randomly selected 240 subjects and tested them for C282Y and H63D mutations using PCR-restriction fragment length polymorphism (RFLP). All 240 randomly selected samples were found to be G/G homozygous non-mutated for C282Y. Of the 240 subjects, 18 (7.5%) were found to be C/G heterozygous and 222 subjects were C/C homozygous non-mutated for H63D. In this study, the C282Y mutation was not found in the Korean population, and the H63D mutation showed allele frequency of 3.8%. The mean TS in this study was higher than that of Caucasians.

Adult↗

Histopathologic Study On Human Sparganosis.

Based on 16 cases of human sparganosis, a histopathological study was made. There was a striking similarity among histological features of sparganosis involving different tissues. The histological change of the affected tissues was characterized by a necrotizing and granulomatous inflammation with or without worm parasite in the lesions. There was also a remarkable polymorphonuclear leukocytic mobilization, predominantly of eosinophils, plasma cells and lymphocytes in and near the lesions. Tunnel formation lined by palisading histiocytes was another charateristic feature of the host tissue reaction. These findings were quite distinguishable from those of cysticercosis which were more localized and self-limited. Several features that were prominent in section slides of sparganum worm parasite were also noted. Laminated calcospherules found in the cytoplasm of the proliferating macrophages and giant cells were of diagnostic value of sparganosis in the absence of the worm, particularly when these were accompanied with tunnel-like lesion in the host tissue.

Journal Article↗

A Histopathological Study On Human Cysticercosis.

A study was made on 258 cases of cysticercosis, that were examined and diagnosed at the Department of Pathology, College of Medicine, Seoul National University during a period of 9 years from 1968 to 1976 inclusive. There were a total of 35,363 surgical specimens examined during the same period, thus revealing the relative frequency ratio of cysticercosis among surgical accessions to be 0.73%. The common sites of involvement of cysticercosis were skeletal muscle, subcutaneous tissue, breast, brain and eye in decreasing order of frequency. Painless palpable nodules were the most common initial presentation clinically. Histopathological staging was attempted based on the host tissue reaction and worm morphology. It was arbitrarily classified into early, intermediate and late stages. In general the morphology of the parasite consisted of a well preserved and compact calcospherules with intact subcuticular muscle layer in the early stage, showing a progressive deterioration of parasitic structures, finally undergoing resorptive process or mummification. The host tissue reation in the early stage was characterized by a diffuse epithelioid cell proliferation with lymphocytic and eosinophilic infiltration without capsule formation. The intermediate stage consisted of a diffuse histiocytic proliferation with well formed outer collagen capsule. The latestage revealed mostly thinned out, well collagenized capsule with scanty lymphocytic infiltration. The parasite in the well formed cyst as usually distorted and often mummified. But the hooklets were relatively preserved up to the late stage. These finding suggest that the host tissue reacts to the cysticercus worm in fairly uniform fashion, and this fashion appears to have a sequence, i.e., violent lymphohistiocytic response in the initial phase of infection, and undergoing a gradual fibrotic (encapsulating) self-limiting course, finally being stabilized by a dense, acelluar collagen capsule or collapse and absorption.

Journal Article↗