Objective: To provide estimates of maternal age-specific rates of fetal chromosomal abnormalities... more Objective: To provide estimates of maternal age-specific rates of fetal chromosomal abnormalities at 16-20 weeks' gestation for Korean women 6 35 years of age. Methods: Using the logistic regression method, we analyzed the amniocentesis data of 2,032 gravidas who had fetal karyotyping for the sole indication of advanced maternal age. Also, we compared the prevalence of trisomy 21 among countries using previously published datasets. Results: The incidence of aneuploidies increased exponentially with maternal age (p ! 0.001). The expected rate of trisomy 21 was 3.7 per 1,000 gravidas at 35 years of age. Comparison with other countries showed that Japan has a significantly lower rate of trisomy 21 than North America (p = 0.041; 95% CI 0.522-0.986) and the UK (p = 0.011; 95% CI 0.474-0.909). Conclusion: These age-related risk figures are the first data for Korean women. Advanced maternal age was in this study ascertained to be a strong risk factor for chromosomal abnormalities; however, the age-specific risk can be influenced by racial factors.
In children with acute leukemia, bone marrow genetic abnormalities (GA) have prognostic significa... more In children with acute leukemia, bone marrow genetic abnormalities (GA) have prognostic significance, and may be the basis for minimal residual disease monitoring. Since April 2007, we have used a multiplex reverse transcriptase-polymerase chain reaction tool (HemaVision) to detect of GA. Methods: In this study, we reviewed the results of HemaVision screening in 270 children with acute leukemia, newly diagnosed at The Catholic University of Korea from April 2007 to December 2011, and compared the results with those of fluorescence in situ hybridization (FISH), and G-band karyotyping. Results: Among the 270 children (153 males, 117 females), 187 acute lymphoblastic leukemia and 74 acute myeloid leukemia patients were identified. Overall, GA was detected in 230 patients (85.2%). HemaVision, FISH, and G-band karyotyping identified GA in 125 (46.3%), 126 (46.7%), and 215 patients (79.6%), respectively. TEL-AML1 (20.9%, 39/187) and AML1-ETO (27%, 20/74) were the most common GA in ALL and AML, respectively. Overall sensitivity of HemaVision was 98.4%, with false-negative results in 2 instances: 1 each for TEL-AML1 and MLL-AF4. An aggregate of diseasesspecific FISH showed 100% sensitivity in detection of GA covered by HemaVision for actual probes utilized. G-band karyotype revealed GA other than those covered by HemaVison screening in 133 patients (49.3%). Except for hyperdiplody and hypodiploidy, recurrent GA as defined by the World Health Organizationthat were not screened by HemaVision, were absent in the karyotype. Conclusion: HemaVision, supported by an aggregate of FISH tests for important translocations, may allow for accurate diagnosis of GA in Korean children with acute leukemia.
Non-albicans Candida species which are resistant to azole are emerging as important pathogens in ... more Non-albicans Candida species which are resistant to azole are emerging as important pathogens in patients with hematological malignancies who received antifungal prophylaxis. C. inconspicua is one of rare Candida spp. and resistant to fluconazole and deep infection ...
We describe the fourth reported case of a de novo 2q33.3–q34 interstitial deletion and review the... more We describe the fourth reported case of a de novo 2q33.3–q34 interstitial deletion and review the literature in attempt to identify relevant candidate genes. A 15‐month‐old female patient presented for evaluation with poor eye contact and developmental delay. She had microcephaly and mild dysmorphic features, such as downslanting palpebral fissures, high forehead, small mouth, high palate, and general hypotonia. At 30 months of age, she was referred to the genetic clinic for an evaluation of persistent developmental delay, autistic traits, and Rett‐like features, including bruxism and repetitive movement of the left hand. Chromosome analysis revealed 46,XX at the 550 band level. No abnormalities were found on analysis of MECP2 gene for Rett syndrome and a DNA methylation test for Prader–Willi syndrome. An array comparative genomic hybridization analysis revealed a de novo 2q33.3–q34 heterozygous deletion (206,048,173–211,980,867). The deletion was estimated to be 5.9 Mb in size and ...
Hypereosinophilia is associated with clonal disorders, reactive conditions, and rarely with idiop... more Hypereosinophilia is associated with clonal disorders, reactive conditions, and rarely with idiopathic hypereosinophilic syndrome (IHES). We investigated whether measurement of eosinophilic activity using the plasma eosinophil cationic protein (ECP) level, interleukin-5 (IL-5) level, and the ratio of eosinophilic cationic protein/eosinophil count (ECP/Eo) could improve the early differentiation among various eosinophilic diseases: IHES (n = 9), clonal disorder (n = 35), reactive eosinophilia with malignancy (n = 30), and reactive eosinophilia with inflammation (n = 46). The 120 eosinophilic patients had higher plasma ECP and IL-5 levels than the non-eosinophilic control group (p <0.05). The 9 patients with IHES had significantly higher plasma ECP and IL-5 levels than patients with other eosinophilic diseases (p <0.05). The plasma levels of ECP and the ECP/Eo ratio were higher in patients with non-haematologic malignancy than in those with other reactive eosinophilias (p <0....
Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by clonal proliferation of... more Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by clonal proliferation of stem cell-like blasts in bone marrow; however, their unique cellular interaction within the bone marrow microenvironment and its functional significance remain unclear. Here, we assessed the bone marrow microenvironment of AML patients and demonstrate that the leukemia stem cells induce a change in the transcriptional programming of the normal mesenchymal stromal cells. The modified leukemic niche alters the expressions of cross-talk molecules (i.e., CXCL-12 and Jagged-1) in mesenchymal stromal cells to provide a distinct cross-talk between normal and leukemia cells, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemoresistance. Of note, AML patients exhibited distinct heterogeneity in the alteration of mesenchymal stroma in bone marrow. The distinct pattern of stromal changes in leukemic bone marrow at initial diagnosis was associated ...
Background : Real-time PCR for quantification of JAK2 V617F has recently been introduced and used... more Background : Real-time PCR for quantification of JAK2 V617F has recently been introduced and used to evaluate the importance of mutant allele burden in both diagnosis and disease progression in myeloproliferative diseases (MPDs). We evaluated the usefulness of JAK2 MutaScreen TM kit that uses a real-time semiquantitative PCR method and has been designed to screen JAK2 V617F mutant allele burden. Methods : Forty MPD patients were included in this study. We screened JAK2 V617F and determined the mutant allele burden using JAK2 MutaScreen TM kit. The mutant allele burden was estimated by six-scaled standards of JAK2 V617F mutant allele (2%, 5%, 12.5%, 31%, 50%, and 78%). For evaluation of test performance, an allele-specific PCR (AS-PCR) was carried out in all samples by using Seeplex JAK2 Genotyping kit. We assessed the clinical differences in distinct disease entities of MPDs according to JAK2 V617F mutant allele burden. Results : JAK2 V617F mutation was detected in 30 cases, including 10 of 11 cases (91%) of polycythemia vera (PV), 13 of 20 cases (65%) of essential thrombocythemia (ET), and 2 of 3 cases (67%) of chronic idiopathic myelofibrosis (CIMF). The concordance rate between the two tests was 95% (38/40). JAK2 V617F mutant allele burden was greater than 50% in 17 cases, and 10 of them (59%) were PV. In contrast, mutant allele burden was less than 50% in 13 cases and 11 of them (85%) were ET. Conclusions : JAK2 MutaScreen TM kit that utilizes a real-time semi-quantitative PCR method is a useful tool for diagnosing MPDs precisely. It can be used to assess the grade of mutant allele burden as well as to screen JAK2 V617F simultaneously.
Multiple epiphyseal dysplasia is a common skeletal dysplasia characterized by mild short stature,... more Multiple epiphyseal dysplasia is a common skeletal dysplasia characterized by mild short stature, early-onset osteoarthritis mainly involving the hip and knee joints, and abnormally small and/or irregular epiphyses. Multiple epiphyseal dysplasia is clinically and genetically heterogeneous and six genes are associated with the phenotype of multiple epiphyseal dysplasia. A 12-year-old Korean boy presented with intermittent knee pain. His height was 144.6 cm (20th percentile) and family history was notable for early-onset osteoarthritis in his father. The proband's x-rays revealed epiphyseal changes characteristic of multiple epiphyseal dysplasia associated with a collagen IX defect, with manifestations primarily restricted to the knees. Mutational analysis identified a novel…
Background : The aberrant, leukemia-associated antigen expression patterns allow us to discrimina... more Background : The aberrant, leukemia-associated antigen expression patterns allow us to discriminate leukemic blasts from normal precursor cells. Our major goal was to determine a guideline for the detection of minimal residual disease using CD20+/CD34+ and myeloid Ag+/CD19+ combination in the bone marrow of acute leukemia in complete remission (CR) after chemotherapy. Methods : Bone marrow samples from 117 patients with acute leukemia in complete remission after chemotherapy and from 22 healthy controls were immunophenotyped by triple staining and measured by flow cytometry. Results : The CD20+/CD34+ cells in the large lymphocyte gate (R1) ranged from 0% to 3.24% (0.8±0.82%, P=0.000) in CD20+/CD34+ B-lineage ALL CR (N=31), from 0.03% to 4.2% (0.7±0.83 %, P=0.000) in CD20-/CD34-B-lineage ALL CR (N=66), from 0.1% to 0.96% (0.45±0.32%, P=0.016) in TALL CR (N=10), and from 0.02% to 0.48% (0.18±0.15%, P=0.776) in AML CR (N=10). The CD13,33+/CD19+ cells in R1 gate ranged from 0% to 2.69% (0.37±0.48%, P<0.001) in CD13,33+/ CD19+ B-lineage ALL CR (N=31), from 0% to 1.8% (0.31±0.28%, P<0.001) in CD13,33-/CD19+ B-lineage ALL CR (N=65), from 0.02% to 0.64% (0.29±0.22%, P=0.071) in TALL CR (N=9), and from 0% to 0.17% (0.07±0.09%, P=0.341) in AML CR (N=3). Conclusions : Using an immunophenotypic method for the detection of early relapse or minimal residual disease of B-lineage ALL bone marrow in CR after chemotherapy, different cutoff values should be applied according to antigen combination and gating. When the proportion of aberrant antigen combination was less than 5% in large lymphocyte gate, the results should be interpreted with caution.
An increase in vancomycin-resistant enterococcal (VRE) bacteremia in hematooncological patients (... more An increase in vancomycin-resistant enterococcal (VRE) bacteremia in hematooncological patients (n=19) in our institution from 2000 through 2001 led us to analyze the molecular epidemiologic patterns and clinical features unique to our cases. The pulsed field gel electrophoresis of the isolates revealed that the bacteremia was not originated from a single clone but rather showed endemic pattern of diverse clones with small clusters. A different DNA pattern of blood and stool isolates from one patient suggested exogenous rather than endogenous route of infection. Enterococcus faecium carrying vanA gene was the causative pathogen in all cases. Patients with VRE bacteremia showed similar clinical courses compared with those with vancomycin-susceptible enterococcal (VSE) bacteremia. Vancomycin resistance did not seem to be a poor prognostic factor because of similar mortality (5/8, 62.5%) noted in VSE bacteremia. Initial disease severity and neutropenic status may be major determinants of prognosis in patients with VRE bacteraemia.
Endothelial progenitor cells (EPCs) have been shown to have therapeutic potential in ischemic dis... more Endothelial progenitor cells (EPCs) have been shown to have therapeutic potential in ischemic disease. However, the number of EPCs for cell therapy is limited. In this study, instead of the typical adherent culture method, we investigated a more efficient, clinically applicable nonadhesive expansion method for early EPCs using cord blood-derived cells to overcome rapid cellular senescence. After a suspension culture of isolated CD34 ؉ cells in serum-free medium containing each cytokine combination was maintained for 9 d, the number of expanded functional EPCs was assessed by an adherent culture assay. Compared to mononuclear cells, the CD34 ؉ fraction was superior in its expansion of functional EPCs that could differentiate into acLDL/UEA-1 ؉ cells without significant cellular senescence, whereas the CD34 ؊ fraction showed no EPC expansion. Among the cytokine combinations tested for the CD34 ؉ fraction, a combination (SFIb) consisting of stem cell factor (SCF), FMS-like tyrosine kinase 3 ligand, interleukin-3, and basic fibroblast growth factor resulted in a reproducible 64-to 1468-fold EPC expansion from various cord blood origins. Interestingly, the SFIb combination displayed markedly increased EPC expansion (2.43-fold), with a higher percentage of CD34 ؉ cells (2.17-fold), undifferentiated blasts (2.38fold) and CXCR4 ؉ cells (1.68-fold) compared to another cytokine combination (SCF, thrombopoietin, and granulocyte colony-stimulating factor), although the two cytokine combinations had a similar level of total mononucleated cell expansion (ϳ10% difference). Accordingly, the cells expanded in the SFIb combination were more effective in recovery of blood flow and neovascularization in hind-limb ischemia in vivo. Taken together, these results suggest that the nonadhesive serum-free culture conditions of the CD34 ؉ fraction provide an effective EPC expansion method for cell therapy, and an expansion condition leading to high percentages of CD34 ؉ cells and blasts is likely important in EPC expansion.-O, E.,
Recent clinical trials using ex vivo expanded mesenchymal stromal cells (MSCs) have raised intere... more Recent clinical trials using ex vivo expanded mesenchymal stromal cells (MSCs) have raised interest in the safety and function of cultured MSCs. Here, to assess the feasibility of using allogenic human umbilical cord blood serum (CBS) for humanized clinical-grade expansion of MSCs, we characterized MSCs expanded in CBS and compared them to MSCs expanded in fetal bovine serum (FBS). MSCs in CBS exhibited a higher preservation of colony-forming cells and an accelerated expansion over serial passages with increased Oct-4 expression compared to those cultured in FBS. Notably, CBS-expanded MSCs exhibited a unique differentiation potential characterized by a shift from adipogenic to osteogenic differentiation. The differentiation shift was associated with enhanced basal and Runx2-mediated transcriptional activation of the osteocalcin promoter, as well as increased accumulation of beta-catenin and the yes-associated protein (YAP) which was independent of changes in TAZ (transcriptional co-activator with PDZ-binding motif) levels. Interestingly, the phenotypes were reversed when the FBS and CBS media were switched, suggesting the unique stimulatory effects of CBS rather than the selection of heterogeneous MSC subpopulations. The distinct regulatory effects of CBS on MSC included selective activation of platelet-derived growth factor and epidermal growth factor signals in MSCs, but not in FBS. Taken together, these results provide insight into the dynamic regulation of MSCs during ex vivo culture and show that the ex vivo culture of MSCs in allogenic human CBS provides a novel tool for the accelerated expansion of a population of MSCs that exhibit a higher self-renewal and an enhanced osteogenic potential.
With contrasting observations on the effects of β-catenin on hematopoietic stem cells (HSCs), the... more With contrasting observations on the effects of β-catenin on hematopoietic stem cells (HSCs), the precise role of Wnt/β-catenin signals on HSC regulation remains unclear. Here, we show a distinct mode of Wnt/β-catenin signal that can regulate HSCs in a stroma-dependent manner. Stabilization of β-catenin in the bone marrow stromal cells promoted maintenance and self-renewal of HSCs in a contact-dependent manner, whereas direct stabilization in hematopoietic cells caused loss of HSCs. Interestingly, canonical Wnt receptors and β-catenin accumulation were predominantly enriched in the stromal rather than the hematopoietic compartment of bone marrows. Moreover, the active form of β-catenin accumulated selectively in the trabecular endosteum in “Wnt 3a-stimulated” or “irradiation-stressed,” but not in “steady-state” marrows. Notably, notch ligands were induced in Wnt/β-catenin activated bone marrow stroma and downstream notch signal activation was seen in the HSCs in contact with the act...
The aims of this study were to investigate centrosome abnormalities in non-small cell lung cancer... more The aims of this study were to investigate centrosome abnormalities in non-small cell lung cancer (NSCLC), and to assess their relationship with DNA aneuploidy, the expression of the cell cycle-associated proteins, and clinicopathological profiles. Tissue microarrays were constructed from 175 NSCLCs. We analyzed centrosome abnormalities and the expression of p16(INK4a), p53, and pRb using immunohistochemistry. Centrosome abnormalities were noted in 29% of the tumors and were even observed in the normal cells adjacent to the tumor. The frequency of DNA aneuploidy was significantly higher in the tumors containing centrosome abnormalities than in the tumors with a normal centrosome. p16(INK4a) expression and loss of pRb expression, but not p53 expression, were significantly associated with centrosome abnormalities. Clinically, centrosome abnormalities were not found to have any prognostic value for NSCLCs. These results suggest that centrosome abnormalities may be associated with inactive pRb-pathway and contribute to pulmonary carcinogenesis by the level of increasing chromosome instability.
Journal of Obstetrics and Gynaecology Research, 2008
A 32-year-old woman at 17 weeks of gestation had a high possibility (1:82) of having a child with... more A 32-year-old woman at 17 weeks of gestation had a high possibility (1:82) of having a child with Down syndrome. Fetal chromosome according to amniocentesis revealed 46,XX,del(7)(q11.23q21.2). The fetus&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; chromosomal defect was not inherent because the chromosome analysis of the parents did not have any abnormal findings. We were regularly monitoring the pregnant woman by routine prenatal schedule and she had a normal spontaneous delivery. The baby showed a typical facial malformation, epicanthal fold, decreased muscle tone, and cardiac abnormalities. This is the first patient prenatally diagnosed with de novo 7q deletion by positive triple marker screening test. We consider the triple test, which is the most popular examination used to clarify the risk of chromosome abnormality in obstetrics, will be used not only for trisomy 21 and 18, but also for any other chromosome abnormalities.
Objective: To provide estimates of maternal age-specific rates of fetal chromosomal abnormalities... more Objective: To provide estimates of maternal age-specific rates of fetal chromosomal abnormalities at 16–20 weeks’ gestation for Korean women ≧35 years of age. Methods: Using the logistic regression method, we analyzed the amniocentesis data of 2,032 gravidas who had fetal karyotyping for the sole indication of advanced maternal age. Also, we compared the prevalence of trisomy 21 among countries using previously published datasets. Results: The incidence of aneuploidies increased exponentially with maternal age (p < 0.001). The expected rate of trisomy 21 was 3.7 per 1,000 gravidas at 35 years of age. Comparison with other countries showed that Japan has a significantly lower rate of trisomy 21 than North America (p = 0.041; 95% CI 0.522–0.986) and the UK (p = 0.011; 95% CI 0.474–0.909). Conclusion: These age-related risk figures are the first data for Korean women. Advanced maternal age was in this study ascertained to be a strong risk factor for chromosomal abnormalities; howeve...
Administration of G-CSF may not always respond in rise of neutrophil counts in different patient ... more Administration of G-CSF may not always respond in rise of neutrophil counts in different patient population. In order to understand a possible interrelationship between the G-CSF and GM-CSF induced leukocyte responses and expression levels of receptors for G-CSF (G-CSFr) and GM-CSF (GM-CSFr), the levels of each receptor and CSF were measured in patients with basophilia (8), eosinophilia (14) and bacterial infection showing neutrophilia (12) in comparison with normal healthy adults (12) and children (14). G-CSFr was expressed in neutrophils in the largest amount followed by monocytes, but GM-CSFr was expressed more in monocytes than neutrophils. Lymphocytes and basophils did not express G-CSFr or GM-CSFr. The amount of GM-CSFr in neutrophils was present less in patients with infection than normal control (P = 0.031). The neutrophils expressed more G-CSFr than GM-CSFr. The quantity of G-CSFr in eosinophil showed marked interval change, higher in acute stage. The plasma concentrations of G-CSF in patients with infection were much higher than normal adults or children (117.95 ± 181.16 pg/ml, P < 0.05). Binding assay with excess amount of CSFs could discriminate the patient who did not show any response to G-CSF or GM-CSF administration. After incubation with excess CSFs, more receptors were blocked in children than in adults (G-CSF P = 0.024, GM-CSF P = 0.006). These results indicate that the amount of CSFr in leukocyte varies in different types of leukocyte, and changes according to the patients' condition even in the same type of leukocyte, and the CSFrs of children bind to CSFs more than those of adults.
missing. Figure 2 showing Orbscan quadmap of both eyes and Figure 3 showing global pachymetry map... more missing. Figure 2 showing Orbscan quadmap of both eyes and Figure 3 showing global pachymetry map by anterior segment-optical coherence tomography (Visante) have been interchanged. Orbscan quadmap picture and postoperative photograph have not been quoted in the text. After making necessary changes, figures will also require renumbering. Financial disclosures/conflicts of interest: The authors do not have any financial interest in the procedure or the drugs used for the patients in this study. The authors did not receive financial support from any source.
Objective: To provide estimates of maternal age-specific rates of fetal chromosomal abnormalities... more Objective: To provide estimates of maternal age-specific rates of fetal chromosomal abnormalities at 16-20 weeks' gestation for Korean women 6 35 years of age. Methods: Using the logistic regression method, we analyzed the amniocentesis data of 2,032 gravidas who had fetal karyotyping for the sole indication of advanced maternal age. Also, we compared the prevalence of trisomy 21 among countries using previously published datasets. Results: The incidence of aneuploidies increased exponentially with maternal age (p ! 0.001). The expected rate of trisomy 21 was 3.7 per 1,000 gravidas at 35 years of age. Comparison with other countries showed that Japan has a significantly lower rate of trisomy 21 than North America (p = 0.041; 95% CI 0.522-0.986) and the UK (p = 0.011; 95% CI 0.474-0.909). Conclusion: These age-related risk figures are the first data for Korean women. Advanced maternal age was in this study ascertained to be a strong risk factor for chromosomal abnormalities; however, the age-specific risk can be influenced by racial factors.
In children with acute leukemia, bone marrow genetic abnormalities (GA) have prognostic significa... more In children with acute leukemia, bone marrow genetic abnormalities (GA) have prognostic significance, and may be the basis for minimal residual disease monitoring. Since April 2007, we have used a multiplex reverse transcriptase-polymerase chain reaction tool (HemaVision) to detect of GA. Methods: In this study, we reviewed the results of HemaVision screening in 270 children with acute leukemia, newly diagnosed at The Catholic University of Korea from April 2007 to December 2011, and compared the results with those of fluorescence in situ hybridization (FISH), and G-band karyotyping. Results: Among the 270 children (153 males, 117 females), 187 acute lymphoblastic leukemia and 74 acute myeloid leukemia patients were identified. Overall, GA was detected in 230 patients (85.2%). HemaVision, FISH, and G-band karyotyping identified GA in 125 (46.3%), 126 (46.7%), and 215 patients (79.6%), respectively. TEL-AML1 (20.9%, 39/187) and AML1-ETO (27%, 20/74) were the most common GA in ALL and AML, respectively. Overall sensitivity of HemaVision was 98.4%, with false-negative results in 2 instances: 1 each for TEL-AML1 and MLL-AF4. An aggregate of diseasesspecific FISH showed 100% sensitivity in detection of GA covered by HemaVision for actual probes utilized. G-band karyotype revealed GA other than those covered by HemaVison screening in 133 patients (49.3%). Except for hyperdiplody and hypodiploidy, recurrent GA as defined by the World Health Organizationthat were not screened by HemaVision, were absent in the karyotype. Conclusion: HemaVision, supported by an aggregate of FISH tests for important translocations, may allow for accurate diagnosis of GA in Korean children with acute leukemia.
Non-albicans Candida species which are resistant to azole are emerging as important pathogens in ... more Non-albicans Candida species which are resistant to azole are emerging as important pathogens in patients with hematological malignancies who received antifungal prophylaxis. C. inconspicua is one of rare Candida spp. and resistant to fluconazole and deep infection ...
We describe the fourth reported case of a de novo 2q33.3–q34 interstitial deletion and review the... more We describe the fourth reported case of a de novo 2q33.3–q34 interstitial deletion and review the literature in attempt to identify relevant candidate genes. A 15‐month‐old female patient presented for evaluation with poor eye contact and developmental delay. She had microcephaly and mild dysmorphic features, such as downslanting palpebral fissures, high forehead, small mouth, high palate, and general hypotonia. At 30 months of age, she was referred to the genetic clinic for an evaluation of persistent developmental delay, autistic traits, and Rett‐like features, including bruxism and repetitive movement of the left hand. Chromosome analysis revealed 46,XX at the 550 band level. No abnormalities were found on analysis of MECP2 gene for Rett syndrome and a DNA methylation test for Prader–Willi syndrome. An array comparative genomic hybridization analysis revealed a de novo 2q33.3–q34 heterozygous deletion (206,048,173–211,980,867). The deletion was estimated to be 5.9 Mb in size and ...
Hypereosinophilia is associated with clonal disorders, reactive conditions, and rarely with idiop... more Hypereosinophilia is associated with clonal disorders, reactive conditions, and rarely with idiopathic hypereosinophilic syndrome (IHES). We investigated whether measurement of eosinophilic activity using the plasma eosinophil cationic protein (ECP) level, interleukin-5 (IL-5) level, and the ratio of eosinophilic cationic protein/eosinophil count (ECP/Eo) could improve the early differentiation among various eosinophilic diseases: IHES (n = 9), clonal disorder (n = 35), reactive eosinophilia with malignancy (n = 30), and reactive eosinophilia with inflammation (n = 46). The 120 eosinophilic patients had higher plasma ECP and IL-5 levels than the non-eosinophilic control group (p <0.05). The 9 patients with IHES had significantly higher plasma ECP and IL-5 levels than patients with other eosinophilic diseases (p <0.05). The plasma levels of ECP and the ECP/Eo ratio were higher in patients with non-haematologic malignancy than in those with other reactive eosinophilias (p <0....
Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by clonal proliferation of... more Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by clonal proliferation of stem cell-like blasts in bone marrow; however, their unique cellular interaction within the bone marrow microenvironment and its functional significance remain unclear. Here, we assessed the bone marrow microenvironment of AML patients and demonstrate that the leukemia stem cells induce a change in the transcriptional programming of the normal mesenchymal stromal cells. The modified leukemic niche alters the expressions of cross-talk molecules (i.e., CXCL-12 and Jagged-1) in mesenchymal stromal cells to provide a distinct cross-talk between normal and leukemia cells, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemoresistance. Of note, AML patients exhibited distinct heterogeneity in the alteration of mesenchymal stroma in bone marrow. The distinct pattern of stromal changes in leukemic bone marrow at initial diagnosis was associated ...
Background : Real-time PCR for quantification of JAK2 V617F has recently been introduced and used... more Background : Real-time PCR for quantification of JAK2 V617F has recently been introduced and used to evaluate the importance of mutant allele burden in both diagnosis and disease progression in myeloproliferative diseases (MPDs). We evaluated the usefulness of JAK2 MutaScreen TM kit that uses a real-time semiquantitative PCR method and has been designed to screen JAK2 V617F mutant allele burden. Methods : Forty MPD patients were included in this study. We screened JAK2 V617F and determined the mutant allele burden using JAK2 MutaScreen TM kit. The mutant allele burden was estimated by six-scaled standards of JAK2 V617F mutant allele (2%, 5%, 12.5%, 31%, 50%, and 78%). For evaluation of test performance, an allele-specific PCR (AS-PCR) was carried out in all samples by using Seeplex JAK2 Genotyping kit. We assessed the clinical differences in distinct disease entities of MPDs according to JAK2 V617F mutant allele burden. Results : JAK2 V617F mutation was detected in 30 cases, including 10 of 11 cases (91%) of polycythemia vera (PV), 13 of 20 cases (65%) of essential thrombocythemia (ET), and 2 of 3 cases (67%) of chronic idiopathic myelofibrosis (CIMF). The concordance rate between the two tests was 95% (38/40). JAK2 V617F mutant allele burden was greater than 50% in 17 cases, and 10 of them (59%) were PV. In contrast, mutant allele burden was less than 50% in 13 cases and 11 of them (85%) were ET. Conclusions : JAK2 MutaScreen TM kit that utilizes a real-time semi-quantitative PCR method is a useful tool for diagnosing MPDs precisely. It can be used to assess the grade of mutant allele burden as well as to screen JAK2 V617F simultaneously.
Multiple epiphyseal dysplasia is a common skeletal dysplasia characterized by mild short stature,... more Multiple epiphyseal dysplasia is a common skeletal dysplasia characterized by mild short stature, early-onset osteoarthritis mainly involving the hip and knee joints, and abnormally small and/or irregular epiphyses. Multiple epiphyseal dysplasia is clinically and genetically heterogeneous and six genes are associated with the phenotype of multiple epiphyseal dysplasia. A 12-year-old Korean boy presented with intermittent knee pain. His height was 144.6 cm (20th percentile) and family history was notable for early-onset osteoarthritis in his father. The proband's x-rays revealed epiphyseal changes characteristic of multiple epiphyseal dysplasia associated with a collagen IX defect, with manifestations primarily restricted to the knees. Mutational analysis identified a novel…
Background : The aberrant, leukemia-associated antigen expression patterns allow us to discrimina... more Background : The aberrant, leukemia-associated antigen expression patterns allow us to discriminate leukemic blasts from normal precursor cells. Our major goal was to determine a guideline for the detection of minimal residual disease using CD20+/CD34+ and myeloid Ag+/CD19+ combination in the bone marrow of acute leukemia in complete remission (CR) after chemotherapy. Methods : Bone marrow samples from 117 patients with acute leukemia in complete remission after chemotherapy and from 22 healthy controls were immunophenotyped by triple staining and measured by flow cytometry. Results : The CD20+/CD34+ cells in the large lymphocyte gate (R1) ranged from 0% to 3.24% (0.8±0.82%, P=0.000) in CD20+/CD34+ B-lineage ALL CR (N=31), from 0.03% to 4.2% (0.7±0.83 %, P=0.000) in CD20-/CD34-B-lineage ALL CR (N=66), from 0.1% to 0.96% (0.45±0.32%, P=0.016) in TALL CR (N=10), and from 0.02% to 0.48% (0.18±0.15%, P=0.776) in AML CR (N=10). The CD13,33+/CD19+ cells in R1 gate ranged from 0% to 2.69% (0.37±0.48%, P<0.001) in CD13,33+/ CD19+ B-lineage ALL CR (N=31), from 0% to 1.8% (0.31±0.28%, P<0.001) in CD13,33-/CD19+ B-lineage ALL CR (N=65), from 0.02% to 0.64% (0.29±0.22%, P=0.071) in TALL CR (N=9), and from 0% to 0.17% (0.07±0.09%, P=0.341) in AML CR (N=3). Conclusions : Using an immunophenotypic method for the detection of early relapse or minimal residual disease of B-lineage ALL bone marrow in CR after chemotherapy, different cutoff values should be applied according to antigen combination and gating. When the proportion of aberrant antigen combination was less than 5% in large lymphocyte gate, the results should be interpreted with caution.
An increase in vancomycin-resistant enterococcal (VRE) bacteremia in hematooncological patients (... more An increase in vancomycin-resistant enterococcal (VRE) bacteremia in hematooncological patients (n=19) in our institution from 2000 through 2001 led us to analyze the molecular epidemiologic patterns and clinical features unique to our cases. The pulsed field gel electrophoresis of the isolates revealed that the bacteremia was not originated from a single clone but rather showed endemic pattern of diverse clones with small clusters. A different DNA pattern of blood and stool isolates from one patient suggested exogenous rather than endogenous route of infection. Enterococcus faecium carrying vanA gene was the causative pathogen in all cases. Patients with VRE bacteremia showed similar clinical courses compared with those with vancomycin-susceptible enterococcal (VSE) bacteremia. Vancomycin resistance did not seem to be a poor prognostic factor because of similar mortality (5/8, 62.5%) noted in VSE bacteremia. Initial disease severity and neutropenic status may be major determinants of prognosis in patients with VRE bacteraemia.
Endothelial progenitor cells (EPCs) have been shown to have therapeutic potential in ischemic dis... more Endothelial progenitor cells (EPCs) have been shown to have therapeutic potential in ischemic disease. However, the number of EPCs for cell therapy is limited. In this study, instead of the typical adherent culture method, we investigated a more efficient, clinically applicable nonadhesive expansion method for early EPCs using cord blood-derived cells to overcome rapid cellular senescence. After a suspension culture of isolated CD34 ؉ cells in serum-free medium containing each cytokine combination was maintained for 9 d, the number of expanded functional EPCs was assessed by an adherent culture assay. Compared to mononuclear cells, the CD34 ؉ fraction was superior in its expansion of functional EPCs that could differentiate into acLDL/UEA-1 ؉ cells without significant cellular senescence, whereas the CD34 ؊ fraction showed no EPC expansion. Among the cytokine combinations tested for the CD34 ؉ fraction, a combination (SFIb) consisting of stem cell factor (SCF), FMS-like tyrosine kinase 3 ligand, interleukin-3, and basic fibroblast growth factor resulted in a reproducible 64-to 1468-fold EPC expansion from various cord blood origins. Interestingly, the SFIb combination displayed markedly increased EPC expansion (2.43-fold), with a higher percentage of CD34 ؉ cells (2.17-fold), undifferentiated blasts (2.38fold) and CXCR4 ؉ cells (1.68-fold) compared to another cytokine combination (SCF, thrombopoietin, and granulocyte colony-stimulating factor), although the two cytokine combinations had a similar level of total mononucleated cell expansion (ϳ10% difference). Accordingly, the cells expanded in the SFIb combination were more effective in recovery of blood flow and neovascularization in hind-limb ischemia in vivo. Taken together, these results suggest that the nonadhesive serum-free culture conditions of the CD34 ؉ fraction provide an effective EPC expansion method for cell therapy, and an expansion condition leading to high percentages of CD34 ؉ cells and blasts is likely important in EPC expansion.-O, E.,
Recent clinical trials using ex vivo expanded mesenchymal stromal cells (MSCs) have raised intere... more Recent clinical trials using ex vivo expanded mesenchymal stromal cells (MSCs) have raised interest in the safety and function of cultured MSCs. Here, to assess the feasibility of using allogenic human umbilical cord blood serum (CBS) for humanized clinical-grade expansion of MSCs, we characterized MSCs expanded in CBS and compared them to MSCs expanded in fetal bovine serum (FBS). MSCs in CBS exhibited a higher preservation of colony-forming cells and an accelerated expansion over serial passages with increased Oct-4 expression compared to those cultured in FBS. Notably, CBS-expanded MSCs exhibited a unique differentiation potential characterized by a shift from adipogenic to osteogenic differentiation. The differentiation shift was associated with enhanced basal and Runx2-mediated transcriptional activation of the osteocalcin promoter, as well as increased accumulation of beta-catenin and the yes-associated protein (YAP) which was independent of changes in TAZ (transcriptional co-activator with PDZ-binding motif) levels. Interestingly, the phenotypes were reversed when the FBS and CBS media were switched, suggesting the unique stimulatory effects of CBS rather than the selection of heterogeneous MSC subpopulations. The distinct regulatory effects of CBS on MSC included selective activation of platelet-derived growth factor and epidermal growth factor signals in MSCs, but not in FBS. Taken together, these results provide insight into the dynamic regulation of MSCs during ex vivo culture and show that the ex vivo culture of MSCs in allogenic human CBS provides a novel tool for the accelerated expansion of a population of MSCs that exhibit a higher self-renewal and an enhanced osteogenic potential.
With contrasting observations on the effects of β-catenin on hematopoietic stem cells (HSCs), the... more With contrasting observations on the effects of β-catenin on hematopoietic stem cells (HSCs), the precise role of Wnt/β-catenin signals on HSC regulation remains unclear. Here, we show a distinct mode of Wnt/β-catenin signal that can regulate HSCs in a stroma-dependent manner. Stabilization of β-catenin in the bone marrow stromal cells promoted maintenance and self-renewal of HSCs in a contact-dependent manner, whereas direct stabilization in hematopoietic cells caused loss of HSCs. Interestingly, canonical Wnt receptors and β-catenin accumulation were predominantly enriched in the stromal rather than the hematopoietic compartment of bone marrows. Moreover, the active form of β-catenin accumulated selectively in the trabecular endosteum in “Wnt 3a-stimulated” or “irradiation-stressed,” but not in “steady-state” marrows. Notably, notch ligands were induced in Wnt/β-catenin activated bone marrow stroma and downstream notch signal activation was seen in the HSCs in contact with the act...
The aims of this study were to investigate centrosome abnormalities in non-small cell lung cancer... more The aims of this study were to investigate centrosome abnormalities in non-small cell lung cancer (NSCLC), and to assess their relationship with DNA aneuploidy, the expression of the cell cycle-associated proteins, and clinicopathological profiles. Tissue microarrays were constructed from 175 NSCLCs. We analyzed centrosome abnormalities and the expression of p16(INK4a), p53, and pRb using immunohistochemistry. Centrosome abnormalities were noted in 29% of the tumors and were even observed in the normal cells adjacent to the tumor. The frequency of DNA aneuploidy was significantly higher in the tumors containing centrosome abnormalities than in the tumors with a normal centrosome. p16(INK4a) expression and loss of pRb expression, but not p53 expression, were significantly associated with centrosome abnormalities. Clinically, centrosome abnormalities were not found to have any prognostic value for NSCLCs. These results suggest that centrosome abnormalities may be associated with inactive pRb-pathway and contribute to pulmonary carcinogenesis by the level of increasing chromosome instability.
Journal of Obstetrics and Gynaecology Research, 2008
A 32-year-old woman at 17 weeks of gestation had a high possibility (1:82) of having a child with... more A 32-year-old woman at 17 weeks of gestation had a high possibility (1:82) of having a child with Down syndrome. Fetal chromosome according to amniocentesis revealed 46,XX,del(7)(q11.23q21.2). The fetus&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; chromosomal defect was not inherent because the chromosome analysis of the parents did not have any abnormal findings. We were regularly monitoring the pregnant woman by routine prenatal schedule and she had a normal spontaneous delivery. The baby showed a typical facial malformation, epicanthal fold, decreased muscle tone, and cardiac abnormalities. This is the first patient prenatally diagnosed with de novo 7q deletion by positive triple marker screening test. We consider the triple test, which is the most popular examination used to clarify the risk of chromosome abnormality in obstetrics, will be used not only for trisomy 21 and 18, but also for any other chromosome abnormalities.
Objective: To provide estimates of maternal age-specific rates of fetal chromosomal abnormalities... more Objective: To provide estimates of maternal age-specific rates of fetal chromosomal abnormalities at 16–20 weeks’ gestation for Korean women ≧35 years of age. Methods: Using the logistic regression method, we analyzed the amniocentesis data of 2,032 gravidas who had fetal karyotyping for the sole indication of advanced maternal age. Also, we compared the prevalence of trisomy 21 among countries using previously published datasets. Results: The incidence of aneuploidies increased exponentially with maternal age (p < 0.001). The expected rate of trisomy 21 was 3.7 per 1,000 gravidas at 35 years of age. Comparison with other countries showed that Japan has a significantly lower rate of trisomy 21 than North America (p = 0.041; 95% CI 0.522–0.986) and the UK (p = 0.011; 95% CI 0.474–0.909). Conclusion: These age-related risk figures are the first data for Korean women. Advanced maternal age was in this study ascertained to be a strong risk factor for chromosomal abnormalities; howeve...
Administration of G-CSF may not always respond in rise of neutrophil counts in different patient ... more Administration of G-CSF may not always respond in rise of neutrophil counts in different patient population. In order to understand a possible interrelationship between the G-CSF and GM-CSF induced leukocyte responses and expression levels of receptors for G-CSF (G-CSFr) and GM-CSF (GM-CSFr), the levels of each receptor and CSF were measured in patients with basophilia (8), eosinophilia (14) and bacterial infection showing neutrophilia (12) in comparison with normal healthy adults (12) and children (14). G-CSFr was expressed in neutrophils in the largest amount followed by monocytes, but GM-CSFr was expressed more in monocytes than neutrophils. Lymphocytes and basophils did not express G-CSFr or GM-CSFr. The amount of GM-CSFr in neutrophils was present less in patients with infection than normal control (P = 0.031). The neutrophils expressed more G-CSFr than GM-CSFr. The quantity of G-CSFr in eosinophil showed marked interval change, higher in acute stage. The plasma concentrations of G-CSF in patients with infection were much higher than normal adults or children (117.95 ± 181.16 pg/ml, P < 0.05). Binding assay with excess amount of CSFs could discriminate the patient who did not show any response to G-CSF or GM-CSF administration. After incubation with excess CSFs, more receptors were blocked in children than in adults (G-CSF P = 0.024, GM-CSF P = 0.006). These results indicate that the amount of CSFr in leukocyte varies in different types of leukocyte, and changes according to the patients' condition even in the same type of leukocyte, and the CSFrs of children bind to CSFs more than those of adults.
missing. Figure 2 showing Orbscan quadmap of both eyes and Figure 3 showing global pachymetry map... more missing. Figure 2 showing Orbscan quadmap of both eyes and Figure 3 showing global pachymetry map by anterior segment-optical coherence tomography (Visante) have been interchanged. Orbscan quadmap picture and postoperative photograph have not been quoted in the text. After making necessary changes, figures will also require renumbering. Financial disclosures/conflicts of interest: The authors do not have any financial interest in the procedure or the drugs used for the patients in this study. The authors did not receive financial support from any source.
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