• Clinical and Experimental Pediatrics
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• v.51 no.6
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• pp.634-639
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• 2008

Purpose : There has been considerable disagreement regarding the most appropriate dosage of gonadotropin-releasing hormone agonist in cases of central precocious puberty. The aim of this study was to determine the appropriate dosage for suppression of the puberty in girls with central precocious or early puberty. Methods : Twenty-two girls with early puberty were randomly subjected to 3 types of dosages of leuprolide acetate for at least 6 months. The number of cases in groups 1, 2, and 3 were 7, 7, and 8, and dosages were 70, 90, and $110{\mu}g/kg/-month$, respectively. Height, weight, bone age, Tanner stage of breast development, and serum levels of LH, FSH, estradiol, and progesterone were measured before treatment and after 6 months of treatment. The number of cases of puberty suppression was compared using a modified puberty suppression score with a nonparametric chi-square test. Results : There were no significant differences of chronologic and bone ages among the groups. There was a significant decrease in height SDS gain after 6 months in group 3 (P<0.05) compared with groups 1 and 2. Serum levels of LH, FSH, estradiol and progesterone were all significantly decreased after treatment in all 3 groups (P<0.05). The number of cases of puberty suppression in each group were 4 (57%), 5 (71%), and 8 (100%). There was a significantly increased proportion of suppression of puberty in group 3 (P<0.05). Conclusion : It was necessary to use a higher dose of gonadotropin-releasing hormone agonist to suppress early puberty in girls; however further longitudinal study will be needed for their prognosis of final adult height.

• Reproductive and Developmental Biology
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• v.29 no.3
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• pp.163-168
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• 2005

The aim of this study was to investigate the changes in insulin-like growth factor-I (IGF-I) and growth hormone (GH) in serum, the quantitation of spermato-genesis and the comparable relationships among these measurements during pubertal period in New Zealand White male rabbits. To investigate the age-related testicular changes in DNA contents of spermatogenic cells, the fine-needle testicular biopsies from males aged 10 to 28 wks were evaluated by flow cytometry(FCM). Body weight increased significantly between the ages of 12 and 20 wks (P<0.05) and reached 3.4 kg at 28 wks of age. The highest serum IGF-I level (451.3ng/mL) was observed at 20wks of age (P<0.05) and thereafter remained stable at low levels. Serum GH level at 18 wks of age was 183.3 pg/mL which was significantly higher compared to the other ages (P<0.05), and the rising time in serum GH tend to be somewhat earlier than that of IGF-I. The relative percentage of It-cells in testicular cell compartments was $48.2\%$ at the age of 18 wks which significantly increased than those of 16-wk-old (P<0.05) and thereafter increased with the advance of age to $68\%$. The percentage of 2C-cells in testis was $26.8\%$ at 18 wks of age which was significantly lower than $54.3\%$ at 16 wks old (P<0.05). The percentage of 4C-cells was constantly maintained $2\~6\%$ except the $9.9\%$ at 18 wks of age. In conclusion, the results suggest that the puberty onset occurred at about the 18 wks of age and that the IGF-I and GH in serum during the pubertal period showed the age/growth-specific changes and these changes might be related to the spermatogenesis. The DNA FCM combined with fine-needle testicular biopsy could offer a very sensitive method to monitor the quantitative spermatogenic events related to the puberty onset.

• Clinical and Experimental Pediatrics
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• v.46 no.4
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• pp.376-381
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• 2003

Purpose : This study aimed to demonstrate the possible pathogenesis of granulopoiesis in patients of Kawasaki disease(KD) using quantitative analysis of G-CSF, GM-CSF and their CSFr. Methods : The plasma levels of G-CSF, GM-CSF, G-CSFr and GM-CSFr were studied in 14 patients in the acute phase of KD; 13 children with normal peripheral white blood cell counts were used as the normal control group. The plasma concentration of G-CSF, GM-CSF were analyzed by ELISA. The G-CSFr and GM-CSFr on the peripheral granulocytes were analyzed by a quantitative flow cytometric assay and QuantiBRITE, and the quantitative changes of receptors which did not combine with G-CSF and GM-CSF were measured. Results : The total number of leukocytes in KD was similar to normal control group, but the leukocytes increased according to the number of neutrophils. The plasma concentration of G-CSF were decreased similar to normal control group(P=0.133), but that of GM-CSF decreased more than the normal control group(P=0.227). The quantity of G-CSFr, GM-CSFr were revealed to be no less than the normal control(P=0.721, P=0.912). After incubation with excessive G-CSF, the expressed G-CSFr on the neutrophils were decreased in both groups(P=0.554). The quantities of expressions of GM-CSFr on the neutrophil after incubation with the excessive GM-CSF were always increased in both groups(P=0.255). The amount of GM-CSFr of neutrophils are in proportion to total white blood cells (r=0.788, P=0.035), but it wasn't in the case of KD(P=0.644). Conclusion : The leukocytosis in KD that mediated by increasing neutrophil was not correlated with the plasma concentrations of G-CSF and GM-CSF, and the amount of expression of G-CSFr and GM-CSFr on granulocyte. It is possible that the reduction of concentration of GM-CSF results by increasing the active GM-CSFr.

• The Journal of Korean Society for Radiation Therapy
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• v.23 no.1
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• pp.59-66
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• 2011

Purpose: Investigation of the clinical use of tangential fields technique using TOMO direct in comparison to conventional LINAC based radiation therapy after breast partial mastectomy. Materials and Methods: Treatment plans were created for 3 left-sided breast cancer patients who had radiation therapy after breast partial mastectomy by using wedged tangential fields technique, field in field technique (FIF), TOMO Direct, TOMO Direct intensity modulated radiation therapy (IMRT) under the normalized prescription condition ($D_{90%}$: 50.4 Gy/28 fx within CTV). Dose volume histogram (DVH) and isodose curve were used to evaluate the dose to the clinical target volume (CTV), organ at risk (OAR). We compared and analyzed dosimetric parameters of CTV and OAR. Dosimetric parameters of CTV are $D_{99}$, $D_{95}$, Dose homogeneity index (DHI: $D_{10}/D_{90}$) and $V_{105}$, $V_{110}$. And dosimetric parameters of OAR are $V_{10}$, $V_{20}$, $V_{30}$, $V_{40}$ of the heart and $V_{10}$, $V_{20}$, $V_{30}$ of left lung. Results: Dosimetric results of CTV, the average value of $D_{99}$, $D_{95}$ were $47.7{\pm}1.1Gy$, $49.4{\pm}0.1Gy$ from wedged tangential fields technique (W) and FIF (F) were $47.1{\pm}0.6Gy$, $49.2{\pm}0.4Gy$. And it was $49.2{\pm}0.4$ vs. $48.6{\pm}0.8Gy$, $49.9{\pm}0.4$ vs. $49.5{\pm}0.3Gy$ Gy for the TOMO Direct (D) and TOMO Direct IMRT (I). The average value of dose homogeneity index was W: $1.1{\pm}0.02$, F: $1.07{\pm}0.02$, D: $1.03{\pm}0.001$, I: $1.05{\pm}0.02$. When we compared the average value of $V_{105}$, $V_{110}$ using each technique, it was the highest as $34.6{\pm}9.3%$, $7.5{\pm}7.9%$ for wedged tangential fields technique and the value dropped for FIF as $16.5{\pm}14.8%$, $2.1{\pm}3.5%$, TOMO direct IMRT as $7.5{\pm}8.3%$, $0.1{\pm}0.1%$ and the TOMO direct showed the lowest values for both as 0%. Dosimetric results of OAR was no significant difference among each technique. Conclusion: TOMO direct provides improved target dose homogeneity over wedged tangential field technique. It is no increase the amount of normal tissue volumes receiving low doses, as oppose to IMRT or Helical TOMO IMRT. Also, it simply performs treatment plan procedure than FIF. TOMO Direct is a clinical useful technique for breast cancer patients after partial mastectomy.

• Journal of Gastric Cancer
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• v.6 no.3
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• pp.154-160
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• 2006

Purpose: According to the 2nd English Edition of the Japanese Gastric Cancer Association (JGCA) in 1998, in case of distal gastric cancer, the 14v (superior mesenteric vein) lymph node (LN) is included in the N2 group. However, in Korea, a modified radical gastrectomy is performed, and a 14v LN dissection is not done as a routine procedure. Thus, we investigated the rate of metastatic 14v LNs, evaluated the necessity of dissection of the 14v LN, and searched for indications of 14v LN dissection. Materials and Methods: From April 2004 to August 2005, we enrolled the patients who were diagnosed as having advanced gastric cancer in the distal third portion of the stomach. We peformed a distal gastrectomy with D2 lymph node dissection as defined in the 2nd English edition of the JGCA classification. We calculated the positive rate of metastatic LNs of each station and analyzed the relationship between the positive rates of No.6 LNs and 14v LNs. We also compared the positive 14v LN group with the negative 14v LN group. Results: The total number of patients was 50, the mean age was 56 (range $30{\sim}80$) years, and sex ratio (Male/Female) was 1.63 : 1. In 47 (94%) cases, distal a gastrectomy with gastroduodenostomy was done, and in the remaining 3 (6%) cases, a distal gastrectomy with gastrojejunostomy was done. The most frequently metastatic LNs were nos. 3 and 6 (54%). The metastatic rate of the f4v LN was 10%, which was similar to that of LN no. 9. In the comparison of the 14v positive group with the 14v negative group, there were significant differences in the numbers of metastatic LNs (mean 25.4 vs 4.91, P<0.001) and the numbers of metastatic no. 6 LNs, (mean 6.8 vs 1.42, P<0.001), and if no. 6 LNs were metastatic, the possibility of metastasis to the 14v LN was 19.2%. In the 14v positive group, all cases were more than stage 3 by the UICC 6th edition. Conclusion: In cases of advanced cancer with metastasis to the no. 6 IN, there was a good chance of metastasis to the 14v LN. Thus, in the operative field, if the tumor is advanced to more than stage 3 by the UICC classification and the no. 6 LN is metastatic, a 14v LN dissection is necessary. However, the usefulness of a 14v LN dissection should be evaluated prospectively through an analysis of tumor recurrence and long-term survival.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.720-732
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• 1995

The use of transforming growth $factor-{\beta}1$ which functions as a potent biologic mediator regulating numerous activities of wound healing has been suggested for the promotion of periodontal regeneration. The mitogenic effects of transforming growth $factor-{\beta}1$ on human periodontal ligament cells and human gingival fibroblasts were evaluated by determining the incorporation of $[^3H]-thymidine$ into DNA of the cells dose-dependently. Cells were prepared with primary cultured fibroblasts and periodontal ligament cells from humans, and used in experiments were the fourth or sixth subpassage. Cells were seeded with serum free Dulbecco's modified Eagle medium containing 0.1% bovine serum albumine. The added concentrations of transforming growth $factor-{\beta}1$ were 0.25, 0.5, 1, 2.5, 5ng/ml and transforming growth $factor-{\beta}1$ were added to the quiescent cells for 24hours, 48hours, 72hours. They were labeled with lnCi/ml $[^3H]$ thymidine for the last 24hour of the each culture. The results were presented as the mean counts per minute (CPM) per well and S.D. of four determinations. The results were as follows. : The DNA synthetic activity of human gingival fibroblasts was increased dose-dependently by transforming growth $factor-{\beta}1$ at 24 hours, 48 hours and 72 hours. The maximum mitogenic effects were at the 48 hour application of transforming growth $factor-{\beta}1$. The DNA synthetic activity was generally more decreased at the 72 hour application than at the 48 hour the application of transforming growth $factor-{\beta}1$. The DNA synthetic activity of human periodontal ligament cells was increased dose-dependently by transforming growth $factor-{\beta}1$ at 24 hours and 48 hours. But the DNA synthetic activity was decreased at 5ng/ml of the 72 hour application. The maximum mitogenic effects were also at the 48 hour application of transforming growth $factor-{\beta}1$. The DNA synthetic activity of human periodontal ligament cells was generally more decreased at the 72 hour application than at the 48 hour application of transforming growth $factor-{\beta}1$. In the comparision of DNA synthetic activity between the human gingival fibroblasts and human periodontal ligament cells, the human gingival fibroblasts had more activity than the human periodontal ligament cells at all time application with the concentration of transforming growth $factor-{\beta}1$. In conclusion, transforming growth $factor-{\beta}1$ has an important roles in the stimulation of DNA synthesis in human periodontal ligament cells and human gingival fibroblasts, which means an increase in collagen synthesizing cells and thus, may be useful for clinical application in periodontal regenerative procedures.

• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.236-249
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• 1993

Background: Among the injurious agents to which the lung airspaces are constantly exposed are reactive species of oxygen. It has been widely believed that reactive oxygen species may be implicated in the etiology of lung injuries. In order to elucidated how this oxidant causes lung cell injury, we investigated the effects of exogenous $H_2O_2$ on alveolar epithelial barrier characteristics. Methods: Rat type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with HEPES-buffered Ringer solution. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against $H_2O_2$ injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ, an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results: These monolayers have a high transepithelial resistance (>2000 ohm-$cm^2$) and actively transport $Na^+$ from apical fluid. $H_2O_2$(0-100 mM) was then delivered to either apical or basolateral fluid. Resulting indicated that $H_2O_2$ decreased Isc and R gradually in dose-dependent manner. The effective concentration of apical $H_2O_2$ at which Isc (or R) was decreased by 50% at one hour ($ED_{50}$) was about 4 mM. However, basolateral $H_2O_2$ exposure led to $ED_{50}$ for Isc (and R) of about 0.04 mM. Inhibition of cellular catalase yielded $ED_{50}$ for Isc (and R) of about 0.4 mM when $H_2O_2$ was given apically, while $ED_{50}$ for basolateral exposure to $H_2O_2$ did not change in the presence of ATAZ. The rate of $H_2O_2$ consumption in apical and basolateral bathing fluids was the same, while cellualr catalase activity rose gradually with time in culture. Conclusion: Our data suggest that basolateral $H_2O_2$ may affect directly membrane component (e.g., $Na^+,\;K^+$-ATPase) located on the basolateral cell surface. Apical $H_2O_2$, on the other hand, may be largely degraded by catalase as it passes through the cells before reaching these membrane components. We conclude that alveolar epithelial barrier integrity as measured by Isc and R are compromised by $H_2O_2$ being relatively sensitive to basolateral (and insensitive to apical) $H_2O_2$.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.317-329
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• 2002

Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.451-463
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• 2006

Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

• Neonatal Medicine
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• v.18 no.1
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• pp.82-88
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• 2011

Purpose: This study aims to describe the clinical characteristics of adrenal insufficiency-associated hypotension in preterm infants and the effects of hydrocortisone therapy on their cardiovascular system and serum electrolytes. Methods: Twelve preterm infants less than 32 gestational weeks admitted to neonatal intensive care unit (NICU) of the Seoul National University Bundang Hospital from January 2007 to August 2009 with clinical and laboratory findings suggestive of adrenal insufficiency were analyzed retrospectively. Results: Gestational age was 27.8${\pm}$2.5 weeks and birth weight was 1,110${\pm}$307 g. Postnatal age, postmenstrual age, weight at the onset of adrenal insufficiency-associated hypotension were 19${\pm}$7 day, 30.6${\pm}$2.4 weeks, 1,285${\pm}$365 g. In preterm infants who showed vasopressor resistance, intravenous hydrocortisone was started with a stress dose of 4 mg/kg/day, maintained for 2.2${\pm}$0.7 days, and then tapered. Serum cortisol concentration before hydrocortisone administration was 11.6${\pm}$4.1 mg/dL. Mean blood pressure increased from 25.0${\pm}$5.4 mmHg to 35.0${\pm}$5.3 mmHg, 38.3${\pm}$8.0 mmHg and 41.9${\pm}$6.5 mmHg at time of hydrocortisone administration and 2, 4 and 6 hours after hydrocortisone administration. Urine output increased from 0.9${\pm}$0.6 mL/kg/hr to 4.1${\pm}$3.4 mL/kg/hr. Twelve hours after the administration of hydrocortisone, dopamine requirement decreased from 11.0${\pm}$2.9 $\mu$g/kg/min to 8.0${\pm}$2.3 $\mu$g/kg/min, and to 5.5${\pm}$3.4 ${\mu}g$/kg/min after 24 hours. Serum sodium concentration was increased from 130${\pm}$4 mEq/L to 136${\pm}$4 mEq/L, serum potassium concentration was decreased from 6.1${\pm}$1.1 mEq/L to 4.6${\pm}$0.6 mEq/L before and 12 hours after hydrocortisone administration. Conclusion: In preterm infants with adrenal insufficiency-associated hypotension, hydrocortisone administration improved blood pressure and urine output, decreased vasopressor requirement, and normalized serum electrolyte abnormalities.