• Analytical Science and Technology
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• v.13 no.4
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• pp.494-503
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• 2000

A 21-residue peptide corresponding to amino acids 84-104 of $p16^{INK4A}$, the tumor suppressor, has been synthesized and its structure was studied by Circular Dichroism, $^1H$ NMR spectroscopy and molecular modeling. A p16-derived peptide (84-104 amino acids) forming stable complex with CDK4 and CDK6 inhibits the ability of CDK4/6 to phosphorylate pRb in vitro, and blocks cell-cycle progression through G1/S phase as shown in the function of the full-length p16. Its NMR spectral data including NOEs, $^3J_{NH-H{\alpha}}$ coupling constants, $C_{\alpha}H$ chemical shift, the average amplitude of amide chemical shift oscillation and temperature coefficients indicate that the secondary structure of a p16-derived peptide is similar to that of the same region of full-length p16, which consists of helix-turn-helix structure. The 3-D distance geometry structure based on NOE-hased distance and torsion angle restraints is characterized by ${\gamma}$-turn conformation between residues $Gly^{89}-Leu^{91}$(${\varphi}_{i+1}=-79.8^{\circ}$, ${\varphi}_{i+1}=60.2^{\circ}$) as evidenced in a single crystal structure for the corresponding region of p18 or p19, but is undefined at both the N and C termini. This compact and rigid ${\gamma}$-turn region is considered to stabilize the structure of p16-derived peptide and serve as a site recognizing cyelin dependent kinase, and this well-defined ${\gamma}$-turn structure could be utilized for the design of anti-cancer drug candidates.

• Analytical Science and Technology
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• v.29 no.4
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• pp.170-178
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• 2016

Accuracy and precision of ID methods for different spike isotopes of ⁷⁶Se, ⁷⁷Se, and ⁷⁸Se were compared for the analysis of Selenium using quadrupole ICP/MS equipped with Octopole reaction cell. From the analysis of Se inorganic standard solution, all of three spikes showed less than 1 % error and 1 % RSD for both short-term (a day) and long-term (several months) periods. They showed similar results with each other and ⁷⁸Se showed was a bit better than ⁷⁶Se and ⁷⁷Se. However, different spikes showed different results when NIST SRM 1568a and SRM 2967 were analyzed because of the several interferences on the m/z measured and calculated. Interferences due to the generation of SeH from ORC was considered as well as As and Br in matrix. The results showed similar accuracy and precisions against SRM 1568a, which has a simple background matrix, for all three spikes and the recovery rate was about 80% with steadiness. The %RSD was a bit higher than inorganic standard (1.8 %, 8.6 %, and 6.3 % for ⁷⁸Se, ⁷⁶Se and ⁷⁷Se, respectively) but low enough to conclude that this experiment is reliable. However, mussel tissue has a complex matrix showed inaccurate results in case of ⁷⁸Se isotope spike (over 100 % RSD). ⁷⁶Se and ⁷⁷Se showd relatively good results of around 98.6 % and 104.2 % recovery rate. The errors were less than 5 % but the precision was a bit higher value of 15 % RSD. This clearly shows that Br interferences are so large that a simple mathematical calibration is not enough for a complex-matrixed sample. In conclusion, all three spikes show similar results when matrix is simple. However, ⁷⁸Se should be avoided when large amount of Br exists in matrix. Either ⁷⁶Se or ⁷⁷Se would provide accurate results.

• Journal of Chest Surgery
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• v.34 no.6
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• pp.447-453
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• 2001

Background: Although pulmonary resection is the standard approach for the management of pulmonary metastases from soft tissue sarcoma, most of them are unresectable and chemotherapy remains the only option. The effectiveness of the cytotoxic drugs may be limited by the toxicities that occur before the therapeutic dose is reached. The regional administration of doxorubicin using pulmonary arterial perfusion in a rodent model can produce 10 to 25 times higher concentrations in the lung than systemic administration with minimal systemic toxicities. However, it is unclear whether a high concentration of doxorubicin has beneficial effects for killing cancer cells. Material and Method: We studied this to evaluate the dose-dependent cytotoxic and apoptotic effects of doxorubicin on methylcholanthrene-induced rat fibrosarcoma(MCA) cells. This study examined the cytotoxicity and apoptosis-related gene expressions(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) in MCA cells after 24 hours exposure to various concentrations of doxorubicin such as 1, 5, 10, 50, and 100 $\mu$M. Result: Dose-dependent cytotoxicity was observed after 24 hours exposure to doxorubicin. However, peak apoptosis after 24 hours exposure was observed at 5 $\mu$M of doxorubicin. Above 5 $\mu$M, apoptotic activity was decreased with dose-increment. All mRNA levels of apoptosis-related genes after 24 hours exposure were up-regulated above the control level at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment except caspase 8, which showed higher levels than the control level at 5 $\mu$M. Apoptosis-related protein levels were highest at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment. However, Bax and Bcl-xL proteins steadily showed higher levels than the control throughout the different concentrations of doxorubicin. Conclusion: These results suggest that apoptosis is the main cytotoxic mechanism in low concentrations of doxorubicin in MCA cells and apoptosis-related genes, such as Bax, caspase 8, and Bcl-xL, are involved. At high concentrations, doxorubicin still can kill MCA cells, even when apoptosis is inhibited, and have its propriety for achieving much cytotoxicity against MCA cells.

• Journal of Chest Surgery
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• v.40 no.6 s.275
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• pp.435-440
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• 2007

Background: Primary malignant lymphoma of the lung is a very rare neoplasm. Although the prognosis of lymphoma is favorable, the clinical features, prognostic factors and management have not been clearly defined. Material and Method: We retrospectively reviewed the records of 8 patients we managed between 1994 and 2000. They all had malignant lymphoma on the pathologic examination of the lung wit no evidence of mediastinal adenopathy and extrathoracic disease, and no past history of lymphoma. Result: The study group consisted of 3 males and 5 female patients with a mean age of 53.9 years. Three patients were asymtomatic and 5 patients were seer with pulmonary or systemic symptoms. The diagnostic methods were 3 CT needle aspiration biopsies, 1 bronchoscopic biopsy and 4 surgical methods (wedge resection, lobectomy). There were 3 patients with MALT lymphoma, two with diffuse large B-cell lymphoma, two with small lymphocytic lymphom, and one with follicular lymphoma. The 8 patients were treated with a variety of modalities, including surgery, chemotherapy, radiotherapy and combination therapy. The 8 patients have survived for a median follow-up of 38 months. Conclusiian: Although this entity of lymphoma appears to have a good prognosis, further clinical experience and long-term follow-up are needed to identify its clinical features, prognostic factors and management.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.311-317
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• 1991

Ten patients with deep muscle-invading bladder carcinoma (clinical stages T3a to T4b) who were not candidates for cystectomy were treated with combined modality treatment with transurethral resection, cisplatin chemotherapy and pelvic irradiation from 1989 through 1990, and were analyzed retrospectively. All patients were not candidates for cystectomy because the tumors were judged unresectable or they were not fit for a radical cystectomy. Of the patients 5 had clinical stage T3a, 3 stage T3b and 2 stage T4b disease. The minimum follow-up was 16 months. The complete response rate is 60$\%$ for all patients. The complete responses were achieved in 4 of 5(80$\%$) with stage cT3a, in 2 of 3(67$\%$)with stage cT3b and in none of 2(0$\%$) with stage cT4b. The partial responses were achieved in 2, so an overall response rate was 80$\%$. All six patients with grade I or II transitional cell carcinoma showed complete responses. Four patients with higher grade tumors showed partial responses in 2 and no response in 2, and all died of their bladder cancer. Six patients who showed complete responses after treatment are alive and only one of them showed a local recurrence 10 months after treatment. Distant metastases developed in 3 patients: lungs in 2(cT4b) of those who were never locally free of disease and spine in 1 patient (cT3b) among those with a partial response. Two patients died of metastases to lungs. During the follow-up diarrhea occurred in one which was improved after conservative treatment. On the basis of this analysis it is suggested that combined modality treatment seems to be a tolerable regimen and can be offered with a relatively high probability of success and conservation of bladder function in those with less advanced tumors by clinical stage and low grade.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.57-63
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• 2010

Purpose: We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). Materials and Methods: From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirtytwo patients (84%) had advanced stage NPC (2002 AJCC Stage III~IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. Results: The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent (${\geq}50%$) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. Conclusion: High Met extent (${\geq}50%$) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.603-613
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• 1995

Plasma progesterone($P_4$) assay has been introduced to apply to the differential diagnosis of reproductive disorders and the monitoring of responses of ovarian dysfunction to $PGF_2{\alpha}$ or GnRH treatment in the 204 postpartum and postinsemination subestrus dairy cows. 1. The incidence rate of reproductive disorders in 204 subestrus cows, diagnosed by palpation per rectum and plasma $P_4$ determination using 'Two sample test'(Day 0+Day 10) were as follows; silent heat or error of estrus detection 110(53.9%), persistent corpus luteum 26(12.7%), follicular cyst 16(7.8%), inactive ovary 12(5.9%), luteal cyst 11(5.4%), granulosa cell tumor of ovary 1(0.5%), fetal mummification 1(0.5%), endometritis 15(7.4%) and pyometra 12(5.9%), respectively. 2. After the $PGF_2{\alpha}$ treatment to the 76 cows with silent heat or error of estrus detection, persistent corpus luteum, or luteal cyst, plasma $P_4$ concentrations at day 3 post treatment using 'Two sample test'(Day 0+Day 3) remained low(<1.0ng/ml) in all 76 cows. Therefore all 76 cows responded positively to $PGF_2{\alpha}$ treatment. Seventeen cows with follicular cyst or inactive ovary were treated with GnRH. All 7 cows with follicular cyst and 4 cows with inactive ovary remained high($${\geq_-}1.0ng/ml$$) a plasma $P_4$ concentrations at day 12 post treatment using 'Two sample test'(Day 0+Day 12), but 6 cows with inactive ovary remained low(<1.0ng/ml) a plasma $P_4$ concentrations. Therefore all 7 cows with follicular cyst and 4 cows with inactive ovary responded positively, but 6 cows with inactive ovary responded negatively to GnRH treatment. 3. The mean days from treatment to first service, number of cows conceived on first service(%), mean number of services per conception, mean days from initial treatment to conception, and mean number of cows conceived by 100 days post treatment(%) were 5.0 and 26.2 days, 45(59.2%) and 6(35.3%) cows, 1.5 and 1.7 services, 13.6 and 22.6 days, and 62(81.6%) and 9(52.9%) cows in group of $PGF_2{\alpha}$ and GnRH treatment, respectively. These results indicated that plasma $P_4$ assay was practical as an aid to diagnosing reproductive disorders and to monitoring responses of ovarian dysfunction to $PGF_2{\alpha}$ and GnRH treatment in subestrus cows.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.1
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• pp.11-18
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• 2002

Purpose: It is known that lactoferrin serves as a source of iron for H. pylori in gastric mucosa. This study was undertaken to investigate the relationship between lactoferrin and H. pylori infection coexistent with iron-deficiency anemia by determining the lactoferrin levels in gastric biopsy specimens, and by locating the major sites of lactoferrin expression, according to the presence or absence of iron-deficiency anemia. Methods: Fifty-five adolescents that underwent gastroduodenoscopy were divided into three groups: NL (n=19) for normal controls, HP (n=15) for patients with H. pylori, and IDA (n=21) for patients with H. pylori gastritis and coexisting iron-deficiency anemia. Histopathologic features were graded from to marked on the basis of the Updated Sydney System. The gastric mucosal levels of lactoferrin were measured by immunoassay. Immunohistochemical technique was used to allow identification of the location and quantification of the lactoferrin expression. Results: Lactoferrin levels in the antrum increased significantly, in proportion to, H. pylori density, polymorphonuclear cell infiltration, and chronic inflammation in the histologic specimens. Patients in the HP and IDA groups showed significantly increased mucosal levels of lactoferrin compared with that observed in the normal group (p=0.0001). The lactoferrin level in IDA group tended to be higher than that in the HP group (p=0.2614). The major sites of lactoferrin expression by immunohistochemistry were in glands and neutrophils within epithelium. Lactoferrin was stained weakly in NL, and strongly in HP and IDA. Conclusion: The lactoferrin sequestration in the gastric mucosa of IDA was remarkable, and this finding seems to give a clue that leads to the clarification of the mechanism by which H. pylori infection contributes to iron-deficiency anemia.

• Pediatric Infection and Vaccine
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• v.16 no.1
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• pp.40-46
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• 2009

Purpose : The purpose of this study was to identify useful predictors for diagnosing bacterial meningitis and performing CSF studies in febrile infants three months or younger. Methods : Six hundred and fifty two febrile infants with a rectal temperature ${\geq}38.0^{\circ}C$ presented from January 2003 to April 2008 and were retrospectively studied. The total white blood cell count (WBC), band count, absolute neutrophil count (ANC), quantitative C-reactive protein (CRP) and blood cultures were performed on admission. The clinical variables associated with bacterial meningitis were analyzed. Results : In patients with bacterial meningitis, the clinical variables including CRP (P=0.036), band count (P=0.037), ANC (P=0.036) and age (P=0.001) were significantly different. The area under the receiver-operating characteristic curve was 0.969 for CRP, 0.946 for the band count, 0.765 for the ANC and 0.235 for age. A CRP cutoff point of 8 mg/dL was determined to maximize both the sensitivity and specificity (sensitivity 83%, specificity 95%, likelihood ratio 16.6). A CRP concentration of <7 mg/dL "ruled-out" bacterial meningitis, with a likelihood ratio of 0.17, a posttest probability of <0.1% and negative predictive value 91%. A CRP concentration greater than 9 mg/dL had a much higher likelihood ratio (20.1) than the band count (16.6) and ANC (2.2). Conclusion : The CRP concentration was a useful laboratory test for the differential diagnosis of bacterial meningitis among febrile infants three months of age or younger. A CRP concentration of <7 mg/dL effectively ruled out bacterial meningitis; a value ${\geq}9mg/dL$ increased the clinical suspicion of bacterial meningitis and the need for CSF evaluation.

• The Korean Journal of Nuclear Medicine Technology
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• v.24 no.1
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• pp.33-38
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• 2020

Purpose Vitamin D is essential for maintaining bone health, controling cell proliferation or differentiation, strengthening immune function by controlling calcium metabolism in the body. Vitamin D deficiency can lead to increase the risk of rickets, osteoporosis, cardiovascular disease, diabetes and cancer. Especially, South Korea is one of the highest population proportion of vitamin D deficiency. Accurate determination of levels of 25-OH-VitD or 25-OH-VitD3 in blood serum is required for the diagnosis and treatment of vitamin D deficiency. In this study, radioimmunoassay of 25-OH-VitD and 25-OH-VitD3 was performed and compared to evaluate the effectiveness of Vitamin D radioimmunoassay. Materials and Methods Serum 25-OH-VitD and 25-OH-VitD3 levels were measured using radioimmunoassay. The interrelationship, reproducibility and population distribution rate were evaluated. In addition, the internal quality control was performed at Asan Medical Center from April 2017 to June 2019 and the result of external quality control (Interagency proficiency evaluation) of first and second half of 2018 hosted by the Korean Society of Nuclear Medicine Technology (KSNMT). Both tests were measured by same manufacturer's reagent. Results 25-OH-VitD showed a strong positive correlation on 97 samples, as 25-OH-VitD3 x 0.9 + 0.3 (R>0.9). In repeated measurement, the average Diff(%) value of the reproducibility evaluation of 25-OH-VitD and 25-OH-VitD3 were 7.7% and 7.4%, respectively. Population distribution results showed no statistically significant differences(p>0.05). The resultant value of internal quality control, which measured from April, 2017 to June 2019 in Blood test room of Nuclear Medicine at Asan Medical Center, showed average (CV%) 6.2% and 6.8%, respectively. As a result of the external quality control (interagency proficiency evaluation) Z value obtained under 2.0, as shown below; Conclusion The interrelationship, reproducibility, population distribution rate, internal quality control and external quality control between 25-OH-VitD and 25-OH-VitD3 radioimmunoassay shows superior outcome. Radioimmunoassay, which can be alone measured in the blood as 25-OH-VitD or 25-OH-VitD3, is considered suitable screening tests for the diagnosis of vitamin D deficiency.