• Analytical Science and Technology
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• v.19 no.1
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• pp.107-114
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• 2006

Early diagnosis and medical intervention are critical for the treatment of patients with metabolic disorders. A rapid analytical method was developed for simultaneous quantification of organic acids and amino acids in urine without labor-intensive pre-extraction procedure showing high sensitivity and specificity. A new method consisted of simple two-step trimethylsilyl (TMS)-trifluoroacetyl (TFA) derivatization using GC/MS-selective ion monitoring (SIM). Filter paper urine specimens were dried under nitrogen after being fortified with internal standard (tropate) in a mixture of distilled water and methanol. Methyl orange was added to the residue as indicator reagent. Silyl derivative of carboxylic functional group was followed by trifluoroacetyl derivative for amino functional group. N-methyl-N-(trimethylsilyl-trifluoroacetamide) and N-methyl-bistrifluoroacetamide were consecutively added and heated for 15-20 min at $65^{\circ}C-70^{\circ}C$, for TMS-TFA derivative, respectively. This reactant was analyzed by GC/MS-SIM. Linear dynamic range showed 0.001-50 mg with the detection limit of (S/N=3) 10-200 ng, and the quantification limit of 80-900 ng in urine. Correlation coefficient of regression line was 0.994-0.998. When the method was applied to the patients 'urine, it clearly differentiated the normal from the patient with metabolic disorder. The study showed that the developed method could be the method of choices in rapid and sensitive screening for organic aciduria and amino acidopathy.

• Journal of Veterinary Science
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• v.24 no.6
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• pp.83.1-83.12
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• 2023

Background: Ellipticine (Ellip.) was recently reported to have beneficial effects on the differentiation of adipose-derived stem cells into mature chondrocyte-like cells. On the other hand, no practical results have been derived from the transplantation of bone marrow stem cells (BMSCs) in a rabbit osteoarthritis (OA) model. Objectives: This study examined whether autologous BMSCs incubated with ellipticine (Ellip.+BMSCs) could regenerate articular cartilage in rabbit OA, a model similar to degenerative arthritis in human beings. Methods: A portion of rabbit articular cartilage was surgically removed, and Ellip.+BMSCs were transplanted into the lesion area. After two and four weeks of treatment, the serum levels of proinflammatory cytokines, i.e., tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2), were analyzed, while macroscopic and micro-computed tomography (CT) evaluations were conducted to determine the intensity of cartilage degeneration. Furthermore, immuno-blotting was performed to evaluate the mitogen-activated protein kinases, PI3K/Akt, and nuclear factor-κB (NF-κB) signaling in rabbit OA models. Histological staining was used to confirm the change in the pattern of collagen and proteoglycan in the articular cartilage matrix. Results: The transplantation of Ellip.+BMSCs elicited a chondroprotective effect by reducing the inflammatory factors (TNF-α, PGE2) in a time-dependent manner. Macroscopic observations, micro-CT, and histological staining revealed articular cartilage regeneration with the downregulation of matrix-metallo proteinases (MMPs), preventing articular cartilage degradation. Furthermore, histological observations confirmed a significant boost in the production of chondrocytes, collagen, and proteoglycan compared to the control group. Western blotting data revealed the downregulation of the p38, PI3K-Akt, and NF-κB inflammatory pathways to attenuate inflammation. Conclusions: The transplantation of Ellip.+BMSCs normalized the OA condition by boosting the recovery of degenerated articular cartilage and inhibiting the catabolic signaling pathway.

• Childhood Kidney Diseases
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• v.27 no.2
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• pp.97-104
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• 2023

Purpose: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria. Methods: This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks. Results: In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period. Conclusions: Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. ClinicalTrials.gov trial registration (NCT0223277)

• International Journal of Stem Cells
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• v.16 no.2
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• pp.215-233
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• 2023

Background and Objectives: MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results: We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions: Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.

• Dementia and Neurocognitive Disorders
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• v.21 no.4
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• pp.147-161
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• 2022

Background and Purpose: Subjective cognitive decline (SCD) refers to the self-perception of cognitive decline with normal performance on objective neuropsychological tests. SCD, which is the first help-seeking stage and the last stage before the clinical disease stage, can be considered to be the most appropriate time for prevention and treatment. This study aimed to compare characteristics between the amyloid positive and amyloid negative groups of SCD patients. Methods: A cohort study to identify predictors for the clinical progression to mild cognitive impairment (MCI) or dementia from subjective cognitive decline (CoSCo) study is a multicenter, prospective observational study conducted in the Republic of Korea. In total, 120 people aged 60 years or above who presented with a complaint of persistent cognitive decline were selected, and various risk factors were measured among these participants. Continuous variables were analyzed using the Wilcoxon rank-sum test, and categorical variables were analyzed using the χ² test or Fisher's exact test. Logistic regression models were used to assess the predictors of amyloid positivity. Results: The multivariate logistic regression model indicated that amyloid positivity on PET was related to a lack of hypertension, atrophy of the left temporal lateral and entorhinal cortex, low body mass index, low waist circumference, less body and visceral fat, fast gait speed, and the presence of the apolipoprotein E ε4 allele in amnestic SCD patients. Conclusions: The CoSCo study is still in progress, and the authors aim to identify the risk factors that are related to the progression of MCI or dementia in amnestic SCD patients through a two-year follow-up longitudinal study.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.2
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• pp.363-368
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• 2014

Purpose : The aim of this study was to appraise properties for radiation therapy techniques and effectiveness of time and economy to a patient in the case of applying flattening filter-free (3F) and flattening filter (2F) beam to the radiation therapy. Materials and Methods : Alderson rando phantom was scanned for computed tomography image. Treatment plans for intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) and stereotactic body radiation therapy (SBRT) with 3F and 2F beam were designed for prostate cancer. To evaluate the differences between the 3F and 2F beam, total monitor units (MUs), beam on time (BOT) and gantry rotation time (GRT) were used and measured with $TrueBeam^{TM}$ STx and Surveillance And Measurement (SAM) 940 detector was used for photoneutron emitted by using 3F and 2F. To assess temporal and economical aspect for a patient, total treatment periods and medical fees were estimated. Results : In using 3F beam, total MUs in IMRT plan increased the highest up to 34.0% and in the test of BOT, GRT and photoneutron, the values in SBRT plan decreased the lowest 39.8, 38.6 and 48.1%, respectively. In the temporal and economical aspect, there were no differences between 3F and 2F beam in all of plans and the results showed that 10 days and 169,560 won was lowest in SBRT plan. Conclusion : According as the results, total MUs increased by using 3F beam than 2F beam but BOT, GRT and photoneutron decreased. From above the results, using 3F beam can decrease intra-fraction setup error and risk of radiation-induced secondary malignancy. But, using 3F beam did not make the benefits of temporal and economical aspect for a patient with the radiation therapy.

• The Journal of the Korean bone and joint tumor society
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• v.9 no.1
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• pp.12-17
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• 2003

Purpose: In this report we are going to discuss about the functional evaluation and the outcome of treatment of metastatic tumor in the lower extremities treated with tumor prosthetic arthroplasty. Materials and Methods: This report is based on nine patients diagnosed as a metastatic tumor and treated by tumor prosthetic arthroplasty, from June 1998 to December 2001. Age of the patients ranged from 49 to 63 with the average of 56.3. The average follow up period was 23.4 months. Two patients had lung cancer, three had breast cancer, two had renal cancer, one colon cancer, and one had multiple myeloma. All these were primary cancers. The site of metastasis were six in proximal femur, two in distal femur, and one in proximal tibia. Tumor excision was performed after biopsy in following the principle of primary tumor management. Excision with wide surgical margin was tried as possible could. Six cases were treated with tumor prosthesis, and the other three cases were reconstructed with bone cement and arthroplasty. Results: The functional evaluation in the extremities at the last follow up was performed on Enneking evaluation score with 6 categories. The highest scored 26, and the lowest scored 10, with an average of 19.5. A case in which the patient died 15 days after the operation was excluded from the evaluation. Among the categories, emotional acceptance to postoperative function and pain relief were highly scored. At the final follow up, seven patients survived, and one colon cancer patient died 68 days after operation. Conclusion: Metastatic tumor occurring in joints of lower extremities could be treated in accordance to the treatment principle of primary tumor. By insertion of tumor prosthesis, we can get satisfactory results of function in the lower extremity and pain relief especially. So, this aspect of medical favor must be considered in treating patients.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.125-135
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• 2001

Purpose : Efforts to predict long-term outcome of focal segmental glomerulosclerosis(FSCS) have been made but have yielded conflicting results. Reports are rare especially in Pediatric patients. In this study, we reviewed the predictable prognostic factors in patients of FSGS Method : Fifty children who diagnosed as biopsy-proven FSGS at department of pediatrics at Yonsei university were studied retrospectively. Based on medical records, response to treatment and pathologic slides, we compared normal renal function group and decreased renal function group, assessed the factors affecting renal survival and progression to renal failure. Results : The mean age at onset was 8 1/12 years, sex ratio was 2.3 : 1, and the mean duration of follow-up was 7 1/12 years. The overall renal survival rate was $34\%$ at 5 years, $8\%$ at 10 years Five-year survival rate was $74\%$ in normal renal function group and $27\%$ in decreased renal function group. Between the two groups, there were no significant differences in age at onset, sex ratio, amount of proteinuria, incidence of hematuria and hypertension, mesangial hypercellularity. Decreased renal function group showed higher serum creatinine level, poor response to treatment, higher percent of glomeruli with sclerosis, moderate to severe tubulointerstitial change and vascular change(P<0.05). The prognostic factors of renal survival rate were same as above and incidence of hypertension also affected renal survival( P<0.05). The progression rate to renal failure did not show statistically significant factor. Conclusion : We reviewed the factors affecting long-term outcome of FSGS. Serum creatinine level, steroid responsiveness, and the degree of glomerulosclerosis were significant prognostic factors. (J Korean Soc Pediatr Nephrol 2001 ;5 : 125-35)

• Korean Journal of Psychosomatic Medicine
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• v.14 no.1
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• pp.62-66
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• 2006

Introduction: Unexpected serious and lethal drug interactions can be occurred by polypharmacy for treatment-resistant psychiatric disorders. We report a case who has suspected upper gastrointestinal bleeding after the combination of clozapine and buspirone. Case : A 69-year-old woman with DSM-IV schizophrenia who was admitted to our hospital had no previous medical problems. Findings on physical exam, laboratory values, EEG, and a magnetic reso-nance imaging scans were no abnormality, except for slightly low level of hemoglobin at admission. Because of aggravating anxiety symptom, a trial of buspirone was begun from 15mg, in addition to olanzapine 30mg. And then olanzapine was switched to clozapine due to her treatment-refractory his-tory and poor response on this admission. Moreover, At the admission 11 weeks later, after 4 weeks of starting buspirone and clozapine, she was placed on a regimen of clozapine 300mg and buspirone 60mg. At this point, she started to complaint nonspecific abdominal pain for 4 days and then hematemesis, melena and hypotension were developed suddenly with negative findings in gastroduodenoscopy. After stopping all medication, the suspected upper gastrointestinal bleeding was subsided. After the regimen was switched back to clozapine only, psychotic symptoms were improved without the recurrence of the adverse events. Conclusion : We concluded that the upper gastrointestinal bleeding in this case was attributed to the drug interaction with clozapine and buspirone, although the definite mechanism is not clear. The clini-cians should be very cautious to prescribe the combination of clozapine and buspirone due to a possible lethal adverse effect.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.15 no.2
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• pp.143-151
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• 2004

Objectives : Child and adolescent onset obsessive compulsive disorder(C-OCD) is known to be associated with poor drug response, high comorbid rate and strong genetic tendencies. Till now studies for C-OCD have been very rare in Korea. We conducted this study to investigate the informations about clinical features, familial psychiatric loading, treatment profiles and course of server C-OCD from the retrospective analysis of inpatient data of Seoul National University Children's Hospital. Method : Retrospective chart review and data analysis was performed. Twenty(male 16 : female 4) patients with final C-OCD diagnosis by DSM-IV at discharge from 1994 to 2002 were found and their medical chart, psychological data, family interview data and nursing reports were collected and analyzed. Results : 1) The sex ratio of C-OCD was male dominant(4:1). 2) Phenomenological, most common obsession was pathologic doubt, contamination fear, followed by aggressive obsession, need for symmetry, sexual obsession, most common compulsion was checking and washing, followed by breathing, movement, symmetry, repetitive asking, hoarding, mental compulsion. 3) Most common comorbid diagnosis was depression. Other axis-I diagnosis associated OCD were anxiety disorder, tic disorder, conduct and oppositional defiant disorder and psychosis. 4) Regarding psychiatric familial loadings, 17 patients(85%) had relatives with psychiatric disorders, OC-spectrum disorders(OCD or OCPD) were found in 9 patients(45%). 5) The majority of patients(75%) have received SSRI and antipsychotics treatment. The response rate above 'moderate improved" by CGI was 75%. 6) During follow-up period in outpatient clinic, five patients(25%) showed continuous complete remission, 10 patients (50%) did residual symptoms with chronic course. Conclusion : This seems to be the first systemic investigation of severe pediatric OCD patients in Korea. The children & adolescents with severe OCD in inpatient-setting showed the high comorbid rate, familial psychiatric loading, and combined pharmacotherapy with antipsychotics, As for symptoms, high rate of aggressive-sexual obsession and atypical compulsions like breathing and moving was reported in this study. Severe pediatric OCD patients, however, responded well to the combined SSRI and antipsychotics regimen.