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1.  Klebsiella pneumoniae liver abscess in an immunocompetent child 
Korean Journal of Pediatrics  2013;56(9):407-410.
Klebsiella pneumoniae has emerged as a leading pathogen that causes pyogenic liver abscesses (PLAs) in Korea. K. pneumoniae liver abscess (KLA) is potentially life threatening, and the diagnosis is difficult. In developed countries, PLA is rarely observed in children and is frequently associated with disorders of granulocyte function and previous abdominal infection. We observed a case of KLA in a healthy 12-year-old boy. To our knowledge, this is the first reported case of KLA in an immunocompetent child without an underlying disease in Korea. The patient was treated with percutaneous catheter drainage and antibiotics. The catheter was placed in the intrahepatic abscess for 3 weeks and parenteral antibiotics (ceftriaxone and amikacin) were administered for 4 weeks, followed by oral antibiotics (cefixime) for 2 weeks. We reported this case to raise awareness of KLA in immunocompetent children among physicians, and to review the diagnosis, risk factors, potential complications, and appropriate treatment of KLA.
doi:10.3345/kjp.2013.56.9.407
PMCID: PMC3819678  PMID: 24223603
Klebsiella pneumoniae; Liver Abscess; Immunity; Child
2.  Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations 
Korean Journal of Pediatrics  2014;57(1):29-34.
Purpose
In this study, we aimed to investigate the prevalence of year-round respiratory viral infection in children with lower respiratory tract infection (LRTI) and the relationship between respiratory viral infection and allergen sensitization in exacerbating asthma.
Methods
We investigated the sources for acute LRTIs in children admitted to our hospital from May 2010 to April 2011. The 6 most common respiratory viruses were isolated from nasopharyngeal aspirate using multiplex reverse transcription-polymerase chain reaction in 309 children; respiratory syncytial virus (RSV), adenovirus (AV), parainfluenza virus (PIV), influenza virus (IFV), human metapneumovirus (hMPV), rhinovirus (RV). Atopic sensitization was defined if more than 1 serum specific Immunoglobulin E level measured using UniCAP (Pharmacia) was over 0.35 IU/mL.
Results
RSV was the most common pathogen of bronchiolitis in hospitalized children through the year. RV or IFV infection was more prevalent in asthma exacerbations compared to other LRTIs. AV and hMPV were more likely to cause pneumonia. RV and IFV were associated with asthma exacerbations in children with atopic sensitization, but not in nonatopic children.
Conclusion
RV and IFV are associated with hospitalization for asthma exacerbation in children with atopic sensitization.
doi:10.3345/kjp.2014.57.1.29
PMCID: PMC3935110  PMID: 24578714
Asthma; Allergens; Child; Orthomyxoviridae; Rhinovirus
3.  A new paradigm in the diagnosis of hereditary hemolytic anemia 
Blood research  2013;48(4):237-239.
doi:10.5045/br.2013.48.4.237
PMCID: PMC3894378  PMID: 24466544
4.  Effects of Diet-Induced Mild Obesity on Airway Hyperreactivity and Lung Inflammation in Mice 
Yonsei Medical Journal  2013;54(6):1430-1437.
Purpose
Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity.
Materials and Methods
We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) β, and tumor necrosis factor (TNF) α in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid.
Results
Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge.
Conclusion
Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma.
doi:10.3349/ymj.2013.54.6.1430
PMCID: PMC3809850  PMID: 24142648
Adipokine; asthma; high fat; vascular endothelial growth factor; transforming growth factor beta; tumor necrosis factor alpha; obesity; airway hyperresponsiveness
5.  Hereditary hemolytic anemia in Korea from 2007 to 2011: A study by the Korean Hereditary Hemolytic Anemia Working Party of the Korean Society of Hematology 
Blood research  2013;48(3):211-216.
Background
The number of patients diagnosed with hereditary hemolytic anemia (HHA) has increased since the advent of novel diagnostic techniques that accurately identify this disorder. Here, we report data from a survey on the prevalence and characteristics of patients diagnosed with HHA in Korea from 2007 to 2011.
Methods
Information on patients diagnosed with HHA in Korea and their clinical and laboratory results were collected using a survey questionnaire. Globin gene and red blood cell (RBC) enzyme analyses were performed. In addition, we analyzed data collected by pediatricians.
Results
In total, 195 cases of HHA were identified. Etiologies identified for HHA were RBC membranopathies, hemoglobinopathies, and RBC enzymopathies, which accounted for 127 (64%), 39 (19.9%), and 26 (13.3%) cases, respectively. Of the 39 patients with hemoglobinopathies, 26 were confirmed by globin gene analysis, including 20 patients with β-thalassemia minor, 5 patients with α-thalassemia minor, and 1 patient with unstable hemoglobin disease.
Conclusion
The number of patients diagnosed with hemoglobinopathies and RBC enzymopathies has increased considerably since the previous survey on HHA in Korea, dated from 1997 to 2006. This is likely the result of improved diagnostic techniques. Nevertheless, there is still a need for more sensitive diagnostic tests utilizing flow cytometry and for better standardization of test results to improve the accuracy of diagnosis of RBC membranopathies in Korea. Additionally, more accurate assays for the identification of RBC enzymopathies are warranted.
doi:10.5045/br.2013.48.3.211
PMCID: PMC3786282  PMID: 24086942
Congenital hemolytic anemia; Hereditary spherocytosis; Thalassemia; Congenital nonspherocytic anemia
6.  Effect of Ex Vivo Culture Conditions on Immunosuppression by Human Mesenchymal Stem Cells 
BioMed Research International  2013;2013:154919.
A microarray analysis was performed to investigate whether ex vivo culture conditions affect the characteristics of MSCs. Gene expression profiles were mainly influenced by the level of cell confluence rather than initial seeding density. The analysis showed that 276 genes were upregulated and 230 genes downregulated in MSCs harvested at ~90% versus ~50% confluence (P < 0.05, FC > 2). The genes that were highly expressed in MSCs largely corresponded to chemotaxis, inflammation, and immune responses, indicating direct or indirect involvement in immunomodulatory functions. Specifically, PTGES and ULBP1 were up-regulated in MSCs harvested at high density. Treatment of MSCs with PTGES or ULBP1 siRNA reversed their inhibition of T-cell proliferation in vitro. The culture conditions such as cell confluence at harvest seem to be important for gene expression profile of MSCs; therefore, the results of this study may provide useful guidelines for the harvest of MSCs that can appropriately suppress the immune response.
doi:10.1155/2013/154919
PMCID: PMC3687591  PMID: 23862134
7.  Human bone marrow-derived mesenchymal stem cell gene expression patterns vary with culture conditions 
Blood research  2013;48(2):107-114.
Background
Because of the heterogeneity of human mesenchymal stem cells (MSCs), methods for cell expansion in culture and the effects on gene expression are critical factors that need to be standardized for preparing MSCs. We investigated gene expression patterns of MSCs with different seeding densities and culture times.
Methods
Bone marrow-derived MSCs were plated at densities from 200 cells/cm2 to 5,000 cells/cm2, and the gene expression patterns were evaluated over time using a reverse-transcription polymerase chain reaction assay.
Results
The mRNA levels of factors that play a critical role in cell migration and tissue regeneration, such as podocalyxin-like protein (PODXL), α4-integrin, α6-integrin, and leukemia inhibitory factor (LIF), were higher in MSCs plated at 200 cells/cm2 than in MSCs plated at 5,000 cells/cm2. The mRNA levels of these factors gradually increased for 10 days and then decreased by day 15 in culture. MSCs seeded at 200 cells/cm2 that were cultured for 10 days expressed high levels of Oct-4 and Nanog. Indoleamine 2,3-dioxygenase, cyclooxygenase-1, and hepatocyte growth factor expression were upregulated in the presence of the proinflammatory cytokine interferon-γ in these cells.
Conclusion
We found differences in the gene expression patterns of MSCs under different culture conditions. MSCs from 10-day cultures seeded at a low density were efficiently expanded, expressed PODXL, α6-integrin, α4-integrin, and LIF, and maintained properties like stemness and immunomodulation. Therefore, ex vivo expansion of MSCs maintained for an adequate culture time after plating at low cell density can provide an effective regenerative medicinal strategy for cell therapies using MSCs.
doi:10.5045/br.2013.48.2.107
PMCID: PMC3698395  PMID: 23826579
Mesenchymal stem cell; Gene expression pattern; Seeding density; Culture time; Cell therapy
8.  Increased Prevalence of H1N1-Induced Severe Lower Respiratory Tract Diseases in Children With Atopic Sensitization 
Purpose
Viral infection is the most common aggravating factor for childhood asthma. Asthma may be a risk factor for severe respiratory symptoms in children with lower respiratory tract infections of viral etiology. Influenza A infection enhances Th2-polarization to house dust mites during the acute phase and leads to lung dysfunction in a mouse model. However, there are no data on the relationship between atopic sensitization and H1N1 (Influenza A) infection in humans. To investigate whether atopic sensitization is associated with the severity of H1N1 pneumonia, we compared clinical features and the atopic sensitization rate between children with and without H1N1 infection.
Methods
Using reverse transcription-polymerase chain reactions, we investigated H1N1 virus infection in 214 children who were hospitalized with high fever and respiratory symptoms from September 2009 to February 2010. We also performed immunoassays for total and specific IgEs to six common aeroallergens. Atopy was defined as positivity for more than one specific IgE. The clinical severity of pneumonia was evaluated based on intensive care unit admission, oxygen therapy, steroid therapy, and atelectasis.
Results
There were 70 H1N1-positive children, 42.9% of whom had pneumonia. Children with H1N1 infection were older and had a higher prevalence of atopic sensitization and pneumonia compared with H1N1-negative children. The rate of atelectasis was higher in children with H1N1 pneumonia than in children with non-H1N1 pneumonia. Among children with H1N1 viral infection, those with atopic sensitization had a higher prevalence of intensive care unit admission and oxygen therapy, and a longer duration of hospitalization than non-atopic children. There were no differences between atopic and non-atopic children without H1N1 viral infection.
Conclusions
The prevalence of H1N1-induced severe lower respiratory tract diseases is higher in children with atopic sensitization.
doi:10.4168/aair.2012.4.5.277
PMCID: PMC3423601  PMID: 22950033
H1N1 virus; atopy; pneumonia; severity; children
9.  Etoposide sensitizes neuroblastoma cells expressing caspase 8 to TRAIL 
TRAIL [TNF (tumour necrosis factor)-related apoptosis-inducing ligand] is a promising agent for clinical use since it kills a wide range of tumour cells without affecting normal cells. We provide evidence that pretreatment with etoposide significantly enhanced TRAIL-mediated apoptosis via up-regulation of DR5 (death receptor 5 or TRAIL-R2) expression in the caspase 8 expressing neuroblastoma cell line, SK-N-MC. In addition, sequential treatment with etoposide and TRAIL increased caspases 8, 9 and 3 activation, Mcl-1 cleavage and Bid truncation, which suggests that the ability of etoposide and TRAIL to induce apoptosis is mediated through activation of an intrinsic signalling pathway. Although TRAIL-R2 expression increased in IMR-32 cells in response to etoposide treatment, cell death was not increased by concurrent treatment with TRAIL compared with etoposide alone, because the cells lacked caspase 8 expression. Restoration of caspase 8 expression by exposure to IFNγ (interferon γ) sensitizes IMR-32 cells to TRAIL. Moreover, pretreatment with etoposide increased TRAIL-induced apoptosis in caspase 8 restored IMR-32 cells through activation of a caspase cascade that included caspases 8, 9 and 3. These results indicate that the etoposide-mediated sensitization of neuroblastoma cells to TRAIL is associated with an increase in TRAIL-R2 expression and requires caspase 8 expression. These observations support the potential use of a combination of etoposide and TRAIL in future clinical trials.
doi:10.1042/CBR20110008
PMCID: PMC3475444  PMID: 23124518
caspase 8; death receptor; etoposide; inferferon γ; mitochondrial cascade; TRAIL; AzaC, 5-aza-2′ deoxycytidine; BCA, bicinchoninic acid; DD, death domain; DcR, decoy receptor; DR5, death receptor 5; FADD, Fas-associated death domain; FBS, fetal bovine serum; IFNγ, interferon γ; NF-κB, nuclear factor κB; PARP, poly(ADP-ribose) polymerase; TNF, tumour necrosis factor; TRAIL, TNF-related apoptosis-inducing ligand
10.  Successful and safe treatment of hemangioma with oral propranolol in a single institution 
Korean Journal of Pediatrics  2012;55(5):164-170.
Purpose
Dramatic improvement of hemangioma to propranolol has been recently reported; however, details on dose and duration of treatment, potential risks, and monitoring have not been determined. The objective of this study is to describe and analyze the use of propranolol as a first-line treatment or as a single therapy in management of complicated hemangioma.
Methods
A retrospective chart review of eight patients diagnosed with hemangioma and treated with propranolol in Kangbuk Samsung Hospital from February 2010 to April 2011 was performed.
Results
Eight patients with hemangioma with functional impairment, cosmetic disfigurement, or rapid growth were treated with propranolol. Five patients had solitary facial hemangioma. The mean age of symptoms at onset was 5 weeks. The median age for starting propranolol treatment was 5.5 months. Propranolol at 2 mg/kg/day was finally administered in divided doses with a gradual increase. Significant regression was observed in seven patients, and shrinkage in size, softening in consistency, and decrease in redness were evident within 4 weeks. Among them, six patients were still taking propranolol, and one patient had stopped after 12 months. Other one patient did not show significant improvement with satisfactory result after 3 months of propranolol use. Treatment with propranolol was well tolerated and had few side effects. No rebound growth was observed in any of the patients.
Conclusion
We observed that use of propranolol was very effective in treatment of hemangioma without obvious adverse effects or relapse.
doi:10.3345/kjp.2012.55.5.164
PMCID: PMC3362730  PMID: 22670151
Hemangioma; Propranolol; Treatment
11.  Peroxisome Proliferator-Activated Receptor-Gamma Expression in the Lung Tissue of Obese Rats 
Yonsei Medical Journal  2011;52(3):495-501.
Purpose
Obesity is a risk factor for asthma and type II diabetes. Peroxisome proliferator-activated receptor (PPAR)-γ has been suggested to regulate inflammatory responses in diabetes and asthma. We investigated whether PPAR-α, PPAR-γ, adiponectin receptors (AdipoR1, AdipoR2), leptin, and tumor necrosis factor (TNF)-α are expressed in rat lung tissues and whether the expression differs between obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) rats.
Materials and Methods
Obese and lean rats were given with a high fat diet or a 30% restricted diet for 32 weeks, and their blood glucose levels and weights were monitored. After 32 weeks, mRNA levels of PPAR-α, PPAR-γ, AdipoR1, AdipoR2, leptin, and TNF-α in lung tissues were measured using real time PCR.
Results
PPAR-α, PPAR-γ, AdipoR1, AdipoR2, leptin, and TNF-α were expressed in both obese and lean rat lung tissues. Increased serum glucose levels on intraperitoneal glucose tolerance testing and a higher weight gain at 32 weeks were observed in OLETF control rats compared to OLETF diet restricted rats. PPAR-γ expression was markedly elevated in obese control and diet restricted rats compared to lean rats, although PPAR-γ expression in obese rats was not affected by diet restriction. Leptin was highly expressed in OLETF rats compared to LETO rats. TNF-α expression was enhanced in OLETF control rats compared LETO diet restricted rats, and decreased by diet restriction. PPAR-α, AdipoR1, and AdipoR2 expression were not significantly different between obese and lean rats.
Conclusion
PPAR-γ was highly expressed in the lung tissues of obese rats and may be a novel treatment target for regulating lung inflammation associated with obesity.
doi:10.3349/ymj.2011.52.3.495
PMCID: PMC3101042  PMID: 21488194
Obesity; peroxisome proliferator activated receptor; adiponectin receptor; lung; leptin; TNF-alpha
12.  Shedding a new light on the HLA matching 
doi:10.5045/kjh.2011.46.1.1
PMCID: PMC3065618  PMID: 21461293
13.  Improved Outcome of Central Nervous System Germ Cell Tumors: Implications for the Role of Risk-adapted Intensive Chemotherapy 
Journal of Korean Medical Science  2010;25(3):458-465.
To determine the impact of treatment protocols on the outcome of central nervous system germ cell tumors (CNS-GCTs), we reviewed the medical records of 53 patients who received front-line chemotherapy from September 1997 to September 2006. Pure germinoma, normal alpha-fetoprotein level and beta-human chorionic gonadotropin level <50 mIU/mL were regarded as low-risk features and the others as high-risk. Patients from different time periods were divided into 3 groups according to the chemotherapy protocols. Group 1 (n=19) received 4 cycles of chemotherapy comprising cisplatin, etoposide and bleomycin. Group 2 (n=16) and group 3 (n=18) received 4 cycles of chemotherapy with cisplatin, etoposide, cyclophosphamide and vincristine in the former and with carboplatin, etoposide, cyclophosphamide and bleomycin in the latter. In group 2 and group 3, high-risk patients received double doses of cisplatin, carboplatin and cyclophosphamide. Radiotherapy was given after chemotherapy according to the clinical requirements. The event-free survivals of groups 1, 2, and 3 were 67.0%, 93.8%, and 100%, respectively (group 1 vs. 2, P=0.06; group 2 vs. 3, P=0.29; group 1 vs. 3, P=0.02). Our data suggest that risk-adapted intensive chemotherapy may improve the outcome of patients with malignant CNS-GCTs.
doi:10.3346/jkms.2010.25.3.458
PMCID: PMC2826748  PMID: 20191048
Neoplasms, Germ Cell and Embryonal; Central Nervous System; Drug Therapy; Survival
14.  The Effect of Interleukin-4 and Amphiregulin on the Proliferation of Human Airway Smooth Muscle Cells and Cytokine Release 
Journal of Korean Medical Science  2008;23(5):857-863.
Airway smooth muscle (ASM) hyperplasia and angiogenesis are important features associated with airway remodeling. We investigated the effect of IL-4 and amphiregulin, an epidermal growth factor family member, on the proliferation of human ASM cells and on the release of vascular endothelial growth factor (VEGF) and monocyte chemotactic protein (MCP)-1 from human ASM cells. Human ASM cells were growth-arrested for 48 hr and incubated with platelet-derived growth factor (PDGF)-BB, interleukin (IL)-4, amphiregulin, and VEGF to evaluate cell proliferation. The cells were treated with PDGF, IL-4 and amphiregulin to evaluate the release of VEGF, MCP-1. IL-4 suppressed unstimulated and PDGF-stimulated ASM cell proliferation. Amphiregulin stimulated ASM cell proliferation in a dose-dependent manner. VEGF did not have any influence on ASM cell proliferation. IL-4 stimulated VEGF secretion by the ASM cells in a dose-dependent manner and showed added stimulatory effects when co-incubated with PDGF. Amphiregulin did not promote VEGF secretion. IL-4 and amphiregulin showed no stimulatory effects on MCP-1 secretion. The results of this study showed that IL-4 had bifunctional effects on airway remodeling, one was the suppression of the proliferation of the ASM cells and the other was the promotion of VEGF release by the ASM cells, and amphiregulin can promote human ASM cell proliferation.
doi:10.3346/jkms.2008.23.5.857
PMCID: PMC2580012  PMID: 18955794
Interleukin-4; Remodeling; Humans, Bronchi; Myocytes, Smooth Muscle; Cell Proliferation; Vascular Endothelial Growth Factor; Amphiregulin
15.  Cotransplanted Bone Marrow Derived Mesenchymal Stem Cells (MSC) Enhanced Engraftment of Hematopoietic Stem Cells in a MSC-dose Dependent Manner in NOD/SCID Mice 
Journal of Korean Medical Science  2006;21(6):1000-1004.
Transplantation of marrow-derived mesenchymal stem cells (MSCs), expanded by culture in addition to whole bone marrow, has been shown to enhance engraftment of human hematopoietic stem cells (HSCs). Our hypothesis was that there might be an optimum ratio range that could enhance engraftment. We examined the percent donor chimerism according to the ratio of HSCs to MSCs in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. We tested a series of ratios of co-transplanted CD34+-selected bone marrow cells, and marrow-derived MSCs into sublethally irradiated NOD/SCID mice. In all experiments, 1×105 bone marrow derived human CD34+ cells were administered to each mouse and human MSCs from different donors were infused concomitantly. We repeated the procedure three times and evaluated engraftment with flow cytometry four weeks after each transplantation. Serial ratios of HSCs to MSCs were 1:0, 1:1, 1:2 and 1:4, in the first experiment, 1:0, 1:1, 1:2, 1:4 and 1:8 in the second and 1:0, 1:1, 1:4, 1:8 and 1:16 in the third. Cotransplantation of HSCs and MSCs enhanced engraftment as the dose of MSCs increased. Our results suggest that the optimal ratio of HSCs and MSCs for cotransplantation might be in the range of 1:8-1:16; whereas, an excessive dose of MSCs might decrease engraftment efficiency.
doi:10.3346/jkms.2006.21.6.1000
PMCID: PMC2721918  PMID: 17179676
Hematopoietic Stem Cells; Mesenchymal Stem Cells; Transplantation; Mice, SCID; Engraftment
16.  Serum Vascular Endothelial Growth Factor in Pediatric Patients with Community-Acquired Pneumonia and Pleural Effusion 
Journal of Korean Medical Science  2006;21(4):608-613.
This study investigated the serum vascular endothelial growth factor (VEGF) levels in children with community-acquired pneumonia. Serum VEGF levels were measured in patients with pneumonia (n=29) and in control subjects (n=27) by a sandwich enzyme-linked immunosorbent assay. The pneumonia group was classified into bronchopneumonia with pleural effusion (n=1), bronchopneumonia without pleural effusion (n=15), lobar pneumonia with pleural effusion (n=4), and lobar pneumonia without pleural effusion (n=9) groups based on the findings of chest radiographs. We also measured serum IL-6 levels and the other acute inflammatory parameters. Serum levels of VEGF in children with pneumonia were significantly higher than those in control subjects (p<0.01). Children with lobar pneumonia with or without effusion showed significantly higher levels of serum VEGF than children with bronchopneumonia. For lobar pneumonia, children with pleural effusion showed higher levels of VEGF than those without pleural effusion. Children with a positive urinary S. pneumonia antigen test also showed higher levels of VEGF than those with a negative result. Serum IL-6 levels did not show significant differences between children with pneumonia and control subjects. Serum levels of VEGF showed a positive correlation with the erythrocyte sedimentation rate in the children with pneumonia. In conclusion, VEGF may be one of the key mediators that lead to lobar pneumonia and parapneumonic effusion.
doi:10.3346/jkms.2006.21.4.608
PMCID: PMC2729879  PMID: 16891801
Vascular Endothelial Growth Factor A; Interleukin-6; Pleural Effusion; Community-Acquired Infections; Pneumonia
17.  Chemoreduction followed by local therapy and adjuvant chemotherapy for advanced intraocular retinoblastoma: a pilot study in a single center. 
Journal of Korean Medical Science  2002;17(6):817-822.
Intraocular (IO) retinoblastoma (RB) has traditionally been treated with enucleation (ENU) or external beam radiotherapy (EBRT). Recently, clinical trials are in progress to cure RB without ENU or EBRT in order to salvage the globe and to avoid unacceptable side effects of EBRT. We performed a pilot study to treat patients with advanced Reese-Ellsworth (RE) stage IO RB with initial chemotherapy (CRx) followed by local therapy (LT) and adjuvant CRx. Ten eyes (8 RE group V, 2 RE group IV) from 9 patients were enrolled from March 2001 to November 2001. All tumors responded to CRx. In 5 of 10 eyes, the RB was enough to be treated with LT after chemoreduction. One patient who underwent LT is waiting for ENU due to post-cryotherapy complication. For a median follow-up of 13 months (8-16 mo), 4 eyes that received LT and adjuvant CRx were relapse-free. A patient with bilateral RB who failed to be a candidate for LT was rescued with high-dose CRx and hematopoietic stem cell transplantation. Consequently, by treating patients according to our strategy, we were able to salvage 6 out of 10 eyes without ENU or EBRT. These results suggest that chemoreduction followed by LT and adjuvant CRx might offer the opportunity to salvage the globe and vision even in patients with advanced stage IO RB.
PMCID: PMC3054962  PMID: 12483008
18.  Double high-dose chemotherapy with autologous stem cell transplantation in patients with high-risk neuroblastoma: a pilot study in a single center. 
Journal of Korean Medical Science  2002;17(4):537-543.
Double high-dose chemotherapy (HDCT) was applied to 18 patients with highrisk neuroblastoma including 14 patients who could not achieve complete response (CR) even after the first HDCT. In 12 patients, successive double HDCT was rescued with peripheral blood stem cells collected during a single round of leukaphereses and in 6 patients, second or more rounds of leukaphereses were necessary after the first HDCT to rescue the second HDCT. The median interval between the first and second HDCT (76 days; range, 47-112) in the single harvest group was shorter than that (274.5 days; range, 83-329) in the double harvest group (p<0.01). Hematologic recovery was slow in the second HDCT. Six (33.3%) treatment-related mortalities (TRM) occurred during the second HDCT but were not related to the shorter interval. Disease-free survival rates at 2 years with a median follow-up of 24 months (range, 6-46) in the single and double harvest group were 57.1% and 33.3%, respectively. These results suggest that successive double HDCT using the single harvest approach may improve the survival of high-risk patients, especially who could not achieve CR after the first HDCT despite delayed hematologic recovery and high rate of TRM during the second HDCT.
PMCID: PMC3054907  PMID: 12172052
19.  Gene Expression Profiles of Human Adipose Tissue-Derived Mesenchymal Stem Cells Are Modified by Cell Culture Density 
PLoS ONE  2014;9(1):e83363.
Previous studies conducted cell expansion ex vivo using low initial plating densities for optimal expansion and subsequent differentiation of mesenchymal stem cells (MSCs). However, MSC populations are heterogeneous and culture conditions can affect the characteristics of MSCs. In this study, differences in gene expression profiles of adipose tissue (AT)-derived MSCs were examined after harvesting cells cultured at different densities. AT-MSCs from three different donors were plated at a density of 200 or 5,000 cells/cm2. After 7 days in culture, detailed gene expression profiles were investigated using a DNA chip microarray, and subsequently validated using a reverse transcription polymerase chain reaction (RT-PCR) analysis. Gene expression profiles were influenced primarily by the level of cell confluence at harvest. In MSCs harvested at ∼90% confluence, 177 genes were up-regulated and 102 genes down-regulated relative to cells harvested at ∼50% confluence (P<0.05, FC>2). Proliferation-related genes were highly expressed in MSCs harvested at low density, while genes that were highly expressed in MSCs harvested at high density (∼90% confluent) were linked to immunity and defense, cell communication, signal transduction and cell motility. Several cytokine, chemokine and growth factor genes involved in immunosuppression, migration, and reconstitution of damaged tissues were up-regulated in MSCs harvested at high density compared with MSCs harvested at low density. These results imply that cell density at harvest is a critical factor for modulating the specific gene-expression patterns of heterogeneous MSCs.
doi:10.1371/journal.pone.0083363
PMCID: PMC3882209  PMID: 24400072

Results 1-19 (19)