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1.  Anatomic Consideration of the C1 Laminar Arch for Lateral Mass Screw Fixation via C1 Lateral Lamina : A Landmark between the Lateral and Posterior Lamina of the C1 
Objective
To clarify the landmark for deciding the entry point for C1 lateral mass screws via the posterior arch by using 3-dimensional (3D) computed images.
Methods
Resnick insisted that the C1 posterior arch could be divided into pure posterior and lateral lamina (C1 pedicle). Authors studied where this transition point (TP) is located between the posterior lamina and the C1 pedicle and how it can be recognized. The 3D computed images of 86 cadaver C1s (M : F=45 : 41) were used in this study.
Results
The superior ridge of the C1 posterior arch had 2 types of orientation. One was in the vertical direction in the C1 posterior lamina and the other was in the horizontal direction in the C1 pedicle. The TP was located at the border between the 2 areas, the same site as the posterior end of the groove of the vertebral artery. On posterior-anterior projection, the posterior arch was sharpened abruptly at TP. We were unable to identify the TP in 6.4% of specimens due to complete or partial osseous bridges. A total of 93.8% of the TP were located between the most enlarged point of the spinal canal and the medial wall of the vertebral artery.
Conclusion
The anatomic entry zone of C1 lateral laminar screws was clarified and identified based on the TP by using preoperative 3D computed images.
doi:10.3340/jkns.2013.54.1.25
PMCID: PMC3772282  PMID: 24044076
Lateral mass screw; Atlas; Lamina; Entry point; Landmark; Preoperative computed tomography
2.  The prevalence of vitamin D deficiency in iron-deficient and normal children under the age of 24 months 
Blood research  2013;48(1):40-45.
Background
Iron and vitamin D deficiencies cause a variety of health issues in children, which might have long-lasting effects even in asymptomatic cases. The present study sought to elucidate the potential association between iron status and serum vitamin D levels in infants.
Methods
We evaluated 102 infants aged 3-24 months who visited the CHA Bundang Medical Center from August 2010 to July 2011. Questionnaire and laboratory data were collected. The infants were classified into iron deficiency anemia (IDA), iron deficiency (ID), and normal groups according to hemoglobin (Hb) and ferritin levels. They were then classified into vitamin D deficiency (VDD), vitamin D insufficiency (VDI), and vitamin D sufficiency (VDS) groups according to 25-hydroxyvitamin D [25(OH)D] levels.
Results
VDD was present in 67% of IDA, 53% of ID, and 29% of normal subjects. The proportion of breastfed infants was the highest in the IDA (97%) and VDD (96%) groups. The odds ratio for the likelihood of iron-deficient infants to have subnormal vitamin D levels was 4.115. There was a significant correlation between Hb and 25(OH)D levels. Plasma 25(OH)D levels were lower in the winter/spring. Body mass index values were higher in the IDA/ID groups. Iron, age, and season were predictors of 25(OH)D levels.
Conclusion
The prevalence of iron and vitamin D deficiency was high in breastfed infants. There was also a significant association between Hb and 25(OH)D levels in infants. Since all breastfed infants should receive vitamin D supplementation, there should also be concern about concurrent deficiencies in infants with IDA.
doi:10.5045/br.2013.48.1.40
PMCID: PMC3624995  PMID: 23589794
Iron deficiency anemia; Vitamin D deficiency; 25(OH)D; Breastfeeding
3.  Prevalence and risk factors for vitamin D deficiency in children with iron deficiency anemia 
Korean Journal of Pediatrics  2012;55(6):206-211.
Purpose
The increasing prevalence of breast feeding has led to concerns about vitamin D deficiency (VDD) and iron deficiency anemia (IDA) in children. We evaluated the prevalence of VDD in a population of Korean children with IDA and assessed the risk factors for VDD in these children.
Methods
A total of 79 children who were diagnosed with IDA were prospectively surveyed from April 2010 to March 2011. Data were collected by questionnaire, medical assessment, and laboratory tests, including measurement of 25-hydroxyvitamin D (25OHD), hemoglobin, and wrist radiography.
Results
The median age was 22 months and 30% of the subjects were female. Over a half of subjects (58%) had subnormal vitamin D level (25OHD<30 ng/mL), and VDD (25OHD<20 ng/mL) was present in 39% of children. There was no difference in serum hemoglobin level between IDA patients with VDD and those without VDD. Most subjects (89%) were currently or had recently been breastfed and almost all subjects (97%) who had VDD received breastfeeding. Children with VDD were more likely to be younger than 2 years, to have been breastfed, and to have been tested in winter or spring. Multivariable analysis indicated seasonal variation was a significant independent risk factor for VDD in our IDA patients.
Conclusion
Our results demonstrated that VDD has a high prevalence in Korean children with IDA. Primary care physicians should be aware of the possibility of VDD in children with IDA and should supplement the vitamin D as well as iron.
doi:10.3345/kjp.2012.55.6.206
PMCID: PMC3382701  PMID: 22745645
Vitamin D deficiency; Iron deficiency anemia; Child
4.  Unilateral Extrapedicular Vertebroplasty and Kyphoplasty in Lumbar Compression Fractures : Technique, Anatomy and Preliminary Results 
Objective
A single balloon extrapedicular kyphoplasty has been introduced as one of the unilateral approaches for thoracic compression fractures; however, the unilateral extrapedicular technique in the lumbar area needs a further understanding of structures in the lumbar area. The purpose of the present study is to describe methods and pitfalls of this procedure based on the anatomy of the lumbar area and to analyze clinical outcome and complications.
Methods
Anatomical evaluation was performed with 2 human cadavers. A retrospective review of unilateral extrapedicular approaches yielded 74 vertebral levels in 55 patients that were treated with unilateral extrapedicular vertebroplasty and kyphoplasty. Radiographic assessment included the restoration rate of vertebral height and correction of kyphosis.
Results
Anatomical evaluation indicates that the safe needle entry zone of bone for the extrapedicular approach was located in the supero-lateral aspect of the junction between the pedicle and vertebral body. The unilateral extrapedicular procedure achieved adequate pain relief with a mean decreases in pain severity of 7.25±1.5 and 2.0±1.4, respectively. Complications were 1 retroperitoneal hematoma, 6 unilateral fillings and 3 epidural leak of the polymethylmethacrylate.
Conclusion
The method of a unilateral extrapedicular approach in kyphoplasty and vertebroplasty in the lumbar area might be similar to that in thoracic approach using a route via the extrapedicular space. However, different anatomical characteristics of the lumbar area should be considered.
doi:10.3340/jkns.2011.49.5.273
PMCID: PMC3115147  PMID: 21716899
Kyphoplasty; Vertebroplasty; Anatomy; Lumbar vertebra; Complications; Outcome
5.  Bystander-Mediated Regression of Murine Neuroblastoma via Retroviral Transfer of the HSV-TK Gene 
Journal of Korean Medical Science  2004;19(1):107-112.
Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We investigated the bystander effect of retrovirusmediated gene transfer of herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblastoma cell line (neuro-2a) in vitro and in vivo, and we examined whether the mechanism of bystander effect in neuroblastoma would also depend on connexin-dependent gap junction and/or immune response. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing. Implanted mixtures of wildtype cells and HSV-TK transduced cells showed a potent bystander effect upon administration of GCV in A/J mice. HSV-TK/GCV system in murine neuroblastoma induced systemic immunity. Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells. In conclusion, a strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma might be dependent on immune response and/or on other mechanism such as protein phosphorylation or transfer of apoptotic vesicle, rather than connexin-dependent gap junction.
doi:10.3346/jkms.2004.19.1.107
PMCID: PMC2822245  PMID: 14966351
Bystander Effect; Neuroblastoma; Gene Therapy
6.  Comparison of Drug-eluting Coronary Stents, Bare Coronary Stents and Self-expanding Stents in Angioplasty of Middle Cerebral Artery Stenoses 
Objective
The purpose of this study is to investigate the results of treatment using stent-angioplasty for symptomatic middle cerebral arterial (MCA) stenosis and comparison of in-stent restenosis between drug-eluting stents (DES), bare metal coronary stents (BMS) and self-expanding stents (SES).
Materials and Methods
From Jan. 2007 to June. 2012, 34 patients (mean age ± standard deviation: 62.9 ± 13.6 years) with MCA stenosis were treated. Inclusion criteria were acute infarction or transient ischemic attacks (TIAs) and angiographically proven symptom related severe stenosis. Stents used for treatment were DES (n = 8), BMS (n = 13) and SES (n = 13). National Institutes of Health Stroke Scale (NIHSS) at admission was 2.5 ± 3.1 and mean stenosis rate was 79.0 ± 8.2%. Assessment of clinical and angiographic results was performed retrospectively.
Results
Among 34 patients, periprocedural complications occurred in four cases (11.8%), however, only two cases (6.0%) were symptomatic. All patients were followed clinically (mean follow-up period; 40.7 ± 17.7 months) and 31 were followed angiographically (91.2%. 13.4 ± 8.5 months). There was no occurrence of repeat stroke in all patients; however, mild TIAs related to restenosis occurred in three of 34 patients (8.8%). The mean NIHSS after stent-angioplasty was 1.7 ± 2.9 and 0.8 ± 1.1 at discharge. The modified Rankin score (mRS) at discharge was 0.5 ± 0.9 and 0.3 ± 0.8 at the last clinical follow-up. In-stent restenosis over 50% occurred in five of 31 angiographically followed cases (16.1%), however, all of these events occurred only in patients who were treated with BMS or SES. Restenosis rate was 0.0% in the DES group and 20.8% in the other group (p = 0.562); it did not differ between BMS and SES (2/11 18.2%, 3/13 23.1%, p = 1.000).
Conclusion
Stent-angioplasty appears to be effective for symptomatic MCA stenosis. As for restenosis, in our study, DES was presumed to be more effective than BMS and SES; meanwhile, the results did not differ between the BMS and SES groups.
doi:10.7461/jcen.2013.15.2.85
PMCID: PMC3704999  PMID: 23844352
Intracranial stenosis; Middle cerebral artery; Restenosis; Stent-angioplasty; Drug-eluting stent; Self-expanding stent
7.  Vitamin D deficiency in infants aged 1 to 6 months 
Korean Journal of Pediatrics  2013;56(5):205-210.
Purpose
The aim of this study was to recognize the state of vitamin D among healthy infants aged 1 to 6 months in South Korea, and also to identify the risk factors affecting the level of vitamin D.
Methods
A total of 117 infants were enrolled in this study for 12 months, from March 1, 2011 to February 29, 2012. Serum levels of 25-hydroxyvitamin D (25[OH]D), calcium, phosphorus, and alkaline phosphatase were measured and data including birth weight, body weight, sex, feeding pattern, delivery mode, siblings and maternal age and occupation were collected. Data was mainly analyzed with independent t-test model.
Results
We determined that the prevalence of vitamin D deficiency (serum 25[OH]D<20 ng/mL [50 mmol/L]) was 48.7% in the population investigated. Particularly in breastfed infants, the prevalence of vitamin D deficiency was strikingly high (90.4%). The mean serum level of 25(OH)D in breastfed infants was lower than that of formula fed infants (9.35 ng/mL vs. 28.79 ng/mL). Also female infants showed lower mean serum level of 25(OH)D than male. Mean serum values of calcium and phosphorus had positive correlation with vitamin D state (P<0.001).
Conclusion
Vitamin D deficiency was found to be very common in infants aged 1 to 6 months in South Korea, and breast feeding was the most critical risk factor of vitamin D deficiency. Therefore we suggest to start vitamin D supplementation in South Korea, as soon as possible, to all infants, including breastfed and female infants.
doi:10.3345/kjp.2013.56.5.205
PMCID: PMC3668201  PMID: 23741234
Breastfeeding; Female infant; Healthy infant; Risk factor; Vitamin D
8.  Morphometric trajectory analysis for the C2 crossing laminar screw technique 
European Spine Journal  2010;19(5):828-832.
This paper reports a morphometric study of the C2 laminae to provide quantitative anatomical data for safe crossing laminar screw placement. A valid trajectory is essential for C2 crossing laminar screw placement. Although several clinical technique notes and modifications to define a safe screw trajectory have been introduced in the recent years, no morphometric analysis has been performed to confirm the accuracy of screw trajectory using this technique. In this study, morphometric analysis was performed on 100 Korean C2 three-dimensional reconstruction CT images. The reconstructive C2 vertebrae from the post-edge of the spinal canal to the spinal process were divided into several zones, 1 mm each. Each zone was chosen as the entry point to imitate a crossing laminar screw (3.5 mm diameter) placement. In each 1-mm zoned trajectory, the screw pass ratio (PR), safe screw angle range (SAR) and maximum screw length (MSL) were measured and compared with the data from the other zoned trajectories. The zone ‘5–6 mm posterior to the post-edge of the spinal canal’ was found to be a more feasible and safer entry point for guiding a crossing laminar screw placement than the other zones because this zone could provide a trajectory with maximal PR (85%), SAR (9.57 ± 4.36º) and a larger MSL (21.74 ± 2.44 mm) than the other areas. The recommended safe screw angle in the axial plane is 49.68 ± 4.94 to 59.19 ± 4.70º. However, the screw angle can vary considerably according to the individual variance. A preoperative evaluation of the screw trajectory is essential for safe screw placement using this technique.
doi:10.1007/s00586-010-1331-z
PMCID: PMC2899951  PMID: 20174836
Cervical vertebra; Crossing laminar screw; Trajectory analysis; Laminar thickness; Entry point; Safe angle
9.  Treatment of Cultured Sebocytes with an EGFR Inhibitor Does Not Lead to Significant Upregulation of Inflammatory Biomarkers 
Annals of Dermatology  2011;23(1):12-18.
Background
Epidermal growth factor receptor (EGFR) inhibitors are being used to treat malignancies originating from epithelia. Unfortunately, blocking the EGFR pathway leads to various side effects, most frequently acneiform eruptions.
Objective
To probe the mechanism underlying this side effect, we investigated the effect of EGFR inhibitors on cultured sebocytes.
Methods
To examine the effects of an EGFR inhibitor (cetuximab, Erbitux® 10 ng/ml) and the effects of EGFR ligands, such as epidermal growth factor (EGF, 10 ng/ml) and transforming growth factor-α (TGF-α, 5 ng/ml), on the production of inflammatory cytokines in cultured sebocytes, we used reverse transcriptase-polymerase chain reaction, immunocytofluorescence and Western blots. Outcomes included the expression of interleukin (IL)-1, IL-6, tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPAR-γ) and EGFR.
Results
There were no significant differences in the expression of IL-1, IL-6, TNF-α, PPAR-γ and EGFR between (a) groups treated with an EGFR inhibitor or an EGFR ligand and (b) the control group, except for a significant increase in the expression of IL-1 in the EGF-treated group.
Conclusion
EGFR inhibitors and EGFR ligands do not provoke the expression of inflammatory biomarkers in cultured sebocytes. The role of the sebaceous glands in EGFR inhibitor-induced acneiform eruption should be investigated more thoroughly.
doi:10.5021/ad.2011.23.1.12
PMCID: PMC3119992  PMID: 21738357
Cultured sebocytes; EGFR inhibitor; Inflammatory biomarkers
10.  Racemose Cysticercosis in the Cerebellar Hemisphere 
Neurocysticercosis is the most common parasitic disease of the central nervous system in humans, caused by infection of the larval stage of the pork tapeworm, Taenia solium. However, cerebellar involvement is rarely reported. We report of a case of racemose cysticercosis in the cerebellar hemisphere. A 44-year-old man presented with headache and dizziness. Magnetic resonance imaging showed hydrocephalus and an ill-defined, multicystic cerebellar mass with hypersignal on T2-weighted images, hyposignal on T1-weighted images and rim enhancement after gadolinium injection. The patient underwent endoscopic third ventriculostomy and the cyst resection was done through a craniotomy. In surgical field, cysts were conglomerated in a dense collagen capsule that were severely adherent to surrounding cerebellar tissue, and transparent cysts contained white, milky fluid. Histological findings confirmed the diagnosis of cysticercosis. He received antiparasitic therapy with praziquantel after surgery. Racemose cysticercosis is rare in the cerebellar hemisphere but neurocysticercosis should be taken into consideration as a differential diagnosis of multiple cystic lesions in the cerebellum.
doi:10.3340/jkns.2010.48.1.59
PMCID: PMC2916149  PMID: 20717513
Cysticercosis; Cerebellum; Cyst
11.  Transmission of Seasonal Outbreak of Childhood Enteroviral Aseptic Meningitis and Hand-foot-mouth Disease 
Journal of Korean Medical Science  2010;25(5):677-683.
This study was conducted to evaluate the modes of transmission of aseptic meningitis (AM) and hand-foot-mouth disease (HFMD) using a case-control and a case-crossover design. We recruited 205 childhood AM and 116 HFMD cases and 170 non-enteroviral disease controls from three general hospitals in Gyeongju, Pohang, and Seoul between May and August in both 2002 and 2003. For the case-crossover design, we established the hazard and non-hazard periods as week one and week four before admission, respectively. In the case-control design, drinking water that had not been boiled, not using a water purifier, changes in water quality, and contact with AM patients were significantly associated with the risk of AM (odds ratio [OR]=2.8, 2.9, 4.6, and 10.9, respectively), while drinking water that had not been boiled, having a non-water closet toilet, changes in water quality, and contact with HFMD patients were associated with risk of HFMD (OR=3.3, 2.8, 6.9, and 5.0, respectively). In the case-crossover design, many life-style variables such as contact with AM or HFMD patients, visiting a hospital, changes in water quality, presence of a skin wound, eating out, and going shopping were significantly associated with the risk of AM (OR=18.0, 7.0, 8.0, 2.2, 22.3, and 3.0, respectively) and HFMD (OR=9.0, 37.0, 11.0, 12.0, 37.0, and 5.0, respectively). Our findings suggest that person-to-person contact and contaminated water could be the principal modes of transmission of AM and HFMD.
doi:10.3346/jkms.2010.25.5.677
PMCID: PMC2858824  PMID: 20436701
Meningitis, Aseptic; Hand, Foot and Mouth Disease; Disease Transmission; Waterborne Infection; Enterovirus; Epidemiology
12.  Efficacy of Low Dose Barbiturate Coma Therapy for the Patients with Intractable Intracranial Hypertension Using the Bispectral™ Index Monitoring 
Objective
Barbiturate coma therapy (BCT) is a useful method to control increased intracranial pressure (IICP) patients. However, the complications such as hypotension and hypokalemia have caused conditions that stopped BCT early. The complications of low dose BCT with Bispectral™ index (BIS) monitoring and those of high dose BCT without BIS monitoring have been compared to evaluate the efficacy of low dose BCT with BIS monitoring.
Methods
We analyzed 39 patients with high dose BCT group (21 patients) and low dose BCT group (18 patients). Because BIS value of 40-60 is general anesthesia score, we have adjusted the target dose of thiopental to maintain the BIS score of 40-60. Therefore, dose of thiopental was kept 1.3 to 2.6 mg/kg/hour during low dose BCT. However, high dose BCT consisted of 5 mg/kg/hour without BIS monitoing.
Results
The protocol of BCT was successful in 72.2% and 38.1% of low dose and high dose BCT groups, respectively. The complications such as QT prolongation, hypotension and cardiac arrest have caused conditions that stopped BCT early. Hypokalemia showed the highest incidence rate in complications of both BCT. The descent in potassium level were 0.63 ± 0.26 in low dose group, and 1.31 ± 0.48 in high dose group. The treatment durations were 4.89 ± 1.68 days and 3.38 ± 1.24 days in low dose BCT and high dose BCT, respectively.
Conclusion
It was proved that low dose BCT showed less severe complications than high dose BCT. Low dose BCT with BIS monitoring provided enough duration of BCT possible to control ICP.
doi:10.3340/jkns.2010.47.4.252
PMCID: PMC2864816  PMID: 20461164
Barbiturate coma therapy; Bispectral™ index (BIS); Thiopental
13.  Surgical Experience of the Ruptured Distal Anterior Cerebral Artery Aneurysms 
Objective
Distal anterior cerebral artery (DACA) aneurysms are fragile and known to have high risks for intraoperative premature rupture and a relatively high associated morbidity. To improve surgical outcomes of DACA aneurysms, we reviewed our surgical strategy and its results postoperatively.
Methods
A total of 845 patients with ruptured cerebral aneurysms were operated in our hospital from January 1991 to December 2005. Twenty-three of 845 patients had ruptured DACA aneurysms which were operated on according to our surgical strategy. Our surgical strategy was as follows; early surgery, appropriate releasing of CSF, appropriate surgical approach, using neuronavigating system, securing the bridging veins, using temporary clipping and/or tentative clipping, meticulous manipulation of aneurysm, and using micro-Doppler flow probe. Twenty of 23 patients who had complete medical records were studied retrospectively. We observed the postoperative radiographic findings and checked Glasgow Outcome Scale score sixth months after the operation.
Results
Nineteen DACA aneurysms were clipped through a unilateral interhemispheric approach and one DACA aneurysm was clipped through a pterional approach. Postoperative radiographic findings revealed complete clipping of aneurysmal neck without stenosis or occlusion of parent arteries. In two patients, a residual neck of aneurysm was visualized. Seventeen patients showed good recovery, one patient resulted in moderate disability, while 2 patients died.
Conclusion
With our surgical strategy it was possible to achieve acceptable surgical morbidity and mortality rates in patients with DACA aneurysms. Appropriate use of tentative clipping, temporary clipping and neuro-navigating systems can give great help for safe approach and clipping of DACA aneurysm.
doi:10.3340/jkns.2007.42.4.281
PMCID: PMC2588209  PMID: 19096557
Distal anterior cerebral artery; Aneurysm; Subarachnoid hemorrhage; Interhemispheric approach; Neuro-navigating system
14.  Analysis of Cellular Changes Resulting from Forced Expression of Dickkopf-1 in Hepatocellular Carcinoma Cells 
Purpose
Recent studies have shown that Dickkopf-1 (DKK-1) is overexpressed in some tumors, including hepatocellular carcinoma. However, the role of increased DKK-1 in these tumors is not known. In this study, the DKK-1 expression in hepatocellular carcinoma (HCC) cell lines was evaluated and the effect of DKK-1 overexpression in HCC cell lines was studied.
Materials and Methods
The expression of DKK-1 in hepatocellular carcinoma cell lines was evaluated by RT-PCR. Stable cell lines that overexpressed DKK-1 were established. Cell growth, adhesion, migration and invasion assays were performed.
Results
RT-PCR analysis showed that 5 out of 8 HCC cell lines expressed DKK-1. The forced expression of DKK-1 suppressed the growth of cells and increased the population of cells in the sub-G1 phase. In addition, DKK-1 reduced the cellular adhesion capacity to collagen type I and fibronectin, and it increased migratory capacity. However, overexpression of DKK-1 did not increase the invasion capacity of the HCC cell line.
Conclusion
Collectively, our data suggest that overexpression of DKK-1 affects the biology of HCC cells.
doi:10.4143/crt.2007.39.1.30
PMCID: PMC2739358  PMID: 19746230
Apoptosis; Cell adhesion; Cell line; Dickkopf-1; Hepatocellular carcinoma
15.  Cavernous Angioma in the Falx Cerebri: A Case Report 
Journal of Korean Medical Science  2006;21(5):950-953.
Intracranial cavernous angiomas are benign vascular malformations and can be divided into intra-axial and extra-axial lesions. Extra-axial cavernous angiomas are relatively rare and usually arise in relation to the dura mater and mimick meningiomas. We report a case of cavernous angioma that occured in the falx cerebri of a 22-yr-old female patient with the special focus on neuroradiologic findings. This is the fourth case of cavernous angioma in the falx cerebri reported in the literature to our knowledge.
doi:10.3346/jkms.2006.21.5.950
PMCID: PMC2722013  PMID: 17043437
Hemangioma; Cavernous Angioma; Hemangioma, Carvenous, Central Nervous System; Falx Cerebri
16.  Temozolomide Chemotherapy in Patients with Recurrent Malignant Gliomas 
Journal of Korean Medical Science  2006;21(4):739-744.
Numerous studies have demonstrated the clinical activity of temozolomide, a second-generation alkylating agent, against malignant brain tumors, however, its activity has not been reported in an Asian population. This study analyzed the efficacy and toxicity of temozolomide in 25 adult patients with recurrent or progressive malignant gliomas after surgery and standard radiation therapy with or without chemotherapy, enrolled in our institution since July 2000. Sixteen patients had glioblastoma multiforme (GBM), six with anaplastic astrocytoma, and three with anaplastic oligodendroglioma. Of the 25 patients, 3 (12%) achieved a complete response (CR), 8 (32%) achieved a partial response (PR), 6 (24%) had stable disease (SD), and 8 (32%) had progressive disease (PD). Two patients achieved a CR, 4 patients achieved a PR, 3 patients had SD and 7 patients had PD in GBM, and 1 patient achieved a CR, 4 patients achieved a PR, 3 patients had SD, 1 patient had PD in the non-GBM patients. Median progression free survival was 8 weeks in GBM and 22 weeks in the non-GBM patients. The median overall survival of each group was 17 weeks and 28 weeks. Temozolomide demonstrated moderate activity in recurrent and progressive malignant gliomas without serious toxicity.
doi:10.3346/jkms.2006.21.4.739
PMCID: PMC2729901  PMID: 16891823
Glioma; Drug Therapy; Recurrence; temozolomide
17.  Pattern of Apoptosis by NS398, a Selective COX-2 Inhibitor, in Hepatocellular Carcinoma Cell Lines 
Purpose
NS398, a selective COX-2 inhibitor, is known to inhibit the growth of COX-2 expressing hepatocellular carcinoma cells. The present study investigated whether the cytotoxic effect of NS398 was COX-2 dependent and whether caspases were involved in NS398-induced apoptosis in hepatocellular carcinoma cells.
Materials and Methods
The expressions of COX-2 in SNU 423 and SNU 449 hepatocellular carcinoma cell lines were examined using RT-PCR and Western blot. The cytotoxic effect of NS398 was measured using MTT in the presence or absence of caspase inhibitors. The distribution of the cell cycle and extent of apoptosis were analyzed using flow cytometry and a Cell Death Elisa kit, respectively.
Results
The expression of COX-2 was observed in SNU423 cells, but not in SNU 449 cells. NS398 treatment resulted in both dose-and time-dependent growth inhibitions, with increases in apoptotic cells in both cell lines. Treatment with the pan-caspase inhibitor, z-VAD- fmk, or the caspase-3 inhibitor, Ac-DMQD-CHO, showed no attenuation of the cytotoxic effect of NS398 in either cell line.
Conclusion
This study demonstrated that the cytotoxic effect of NS398 was independent of COX-2 expression. Caspases were also shown not to be involved in NS398-induced apoptosis in either SNU 423 or SNU 449 Korean HCC cell lines. Our data suggests the feasibility of preventing hepatocellular carcinoma with the use of COX-2 inhibitors needs to be carefully evaluated.
doi:10.4143/crt.2005.37.5.313
PMCID: PMC2785925  PMID: 19956533
Apoptosis; Cyclooxygenase 2; Hepatocellular carcinoma; NS398
18.  Limited Effect of CpG ODN in Preventing Type 1 Diabetes in NOD Mice 
Yonsei Medical Journal  2005;46(3):341-346.
Type 1 diabetes is considered as Th1 cell mediated autoimmune disease and the suppression of Th1 cells or the activation of Th2 cells has been regarded as a plausible immunologic intervention for the prevention of type 1 diabetogenesis in a rodent model. CpG ODN is an immunostimulatory sequence primarily present in bacterial DNA, viral DNA and BCG. CpG ODN is conventionally classified as a Th1 cell activator, which has been clinically applied to cancer, allergy and infectious disease. Recently, there was a promising report of that CpG ODN administration suppressed the development of type 1 diabetes in NOD mice by inducing Th2 cell mediated cytokine. However, the antidiabetogenic effect of CpG ODN on NOD mice is controversial. Thus, two studies were serially undertaken with various kinds of CpG motif to find a more optimal sequence and administration method. In the first study, CpG ODN was vaccinated four times and pancreatic inflammation and the quantity of serum insulin subsequently evaluated. In the second study, the amounts of IFN γ and IL-4 in sera were measured as representative cytokines of Th1 and Th2 cells, respectively. As a result, vaccination or continuous injection of CpG ODN failed to show a preventive effect on type 1 diabetogenesis in NOD mice. Structural differences of CpG ODN also had no affect on the result. CpG ODN also consistently showed affect on the pancreatic pathology. The productions of IFN and IL-4 were γ detected only in the K and D type CpG ODN administration groups. Comparison of the two cytokines leads to the conclusion that CpG ODN generated a Th1-weighted response in both study groups. It was assumed that CpG ODN failed to produce Th2-weighted cytokine milieu, which can overcome the genetically determined phenotype of NOD mice. Given these results, it was concluded that the immunotherapeutic application of CpG ODN on Type 1 diabetes had clear limitations.
doi:10.3349/ymj.2005.46.3.341
PMCID: PMC2815809  PMID: 15988804
Type 1 diabetes; CpG ODN; NOD mice; Th1/Th2 balance
19.  The pattern of differentially expressed genes in biliary atresia. 
Journal of Korean Medical Science  2003;18(3):392-396.
Biliary atresia is a progressive obliterative cholangiopathy, but the etiology of this disorder remains uncertain. Identifying genes specifically expressed in biliary atresia and analyzing the pattern of expression may lead to a better understanding of the pathogenesis. Liver tissues were taken from a recipient with biliary atresia and a normal donor during liver transplantation. Total RNA was extracted from each sample and reversely transcribed to cDNA. Then radiolabeled cDNA probe pools were made by random primed DNA labeling method and used for screening of differentially expressed genes by hybridizing with expressed sequence tags (EST) dot blot panel. Northern blot hybridization was done to confirm that these genes are also differentially expressed in other liver tissues. Among 1730 EST clones, 26 cDNA clones were significantly overexpressed in biliary cirrhosis, while 2 clones were significantly decreased in biliary atresia. By Northern blot hybridization, the results of tissue inhibitor of metalloproteinase (TIMP)-1 and IGFBP-2 were well correlated with differential EST screening (DES). This study identified the pattern of differentially expressed genes in the biliary cirrhosis due to biliary atresia using DES technique.
PMCID: PMC3055047  PMID: 12808327
20.  Autologous stem cell transplantation for the treatment of neuroblastoma in Korea. 
Journal of Korean Medical Science  2003;18(2):242-247.
Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.
PMCID: PMC3055035  PMID: 12692423
21.  Autoimmune hemolytic anemia predominantly associated with IgA anti-E and anti-c. 
Journal of Korean Medical Science  2002;17(5):708-711.
A patient with warm autoimmune hemolytic anemia (AIHA) due to predominance of immunoglobulin A (IgA) with an Rh specificity, considered to be the first case in Korea, is described. A 13-year-old male patient with severe hemolytic anemia showed a weak reactivity (1+) in the direct antiglobulin test (DAT) by using anti-IgG antiglobulin reagent. This finding, however, could not fully explain the patient's severe AIHA. When anti-IgA reagent was used for the DAT, strong reactivity (4+) was observed and free anti-E and anti-c autoantibodies were also detected by anti-IgA and anti-IgG reagents. The patient's hemoglobin began to rise with the administration of steroids. Because RBCs coated with multiple types of immunoglobulins are associated with more severe hemolysis than those only with IgG, the DATs using anti-IgA and other reagents are needed for the correct diagnosis when the result of DAT is not compatible with patient's clinical manifestations.
PMCID: PMC3054947  PMID: 12378029
22.  Umbilical Cord Blood Therapy Potentiated with Erythropoietin for Children with Cerebral Palsy: A Double-blind, Randomized, Placebo-Controlled Trial 
Stem Cells (Dayton, Ohio)  2012;31(3):581-591.
Allogeneic umbilical cord blood (UCB) has therapeutic potential for cerebral palsy (CP). Concomitant administration of recombinant human erythropoietin (rhEPO) may boost the efficacy of UCB, as it has neurotrophic effects. The objectives of this study were to assess the safety and efficacy of allogeneic UCB potentiated with rhEPO in children with CP. Children with CP were randomly assigned to one of three parallel groups: the pUCB group, which received allogeneic UCB potentiated with rhEPO; the EPO group, which received rhEPO and placebo UCB; and the Control group, which received placebo UCB and placebo rhEPO. All participants received rehabilitation therapy. The main outcomes were changes in scores on the following measures during the 6 months treatment period: the gross motor performance measure (GMPM), gross motor function measure, and Bayley scales of infant development-II (BSID-II) Mental and Motor scales (18). F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) and diffusion tensor images (DTI) were acquired at baseline and followed up to detect changes in the brain. In total, 96 subjects completed the study. Compared with the EPO (n = 33) and Control (n = 32) groups, the pUCB (n = 31) group had significantly higher scores on the GMPM and BSID-II Mental and Motor scales at 6 months. DTI revealed significant correlations between the GMPM increment and changes in fractional anisotropy in the pUCB group. 18F-FDG-PET/CT showed differential activation and deactivation patterns between the three groups. The incidence of serious adverse events did not differ between groups. In conclusion, UCB treatment ameliorated motor and cognitive dysfunction in children with CP undergoing active rehabilitation, accompanied by structural and metabolic changes in the brain. Stem Cells2013;31:581–591
doi:10.1002/stem.1304
PMCID: PMC3744768  PMID: 23281216
Umbilical cord blood; Erythropoietin; Cerebral palsy; Clinical trial; Function

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