• Journal of Life Science
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• v.19 no.6
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• pp.770-780
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• 2009

A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a), was derived from Spirulina platensis. We conducted a series of experiments, in vitro and in vivo, to evaluate the anticancer effect and mechanism of photodynamic therapy using 9-HpbD-a and 660 nm diode lasers on a squamous carcinoma cell line. We studied the cytotoxic effects of pheophytin-a, 9-HpbD-a, 9-HpbD-a red and 660 nm diode lasers in a human head and neck cancer cell line (SNU-1041). Cell growth inhibition was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of 9-HpbD was higher than those of 9-HpbD-a red or pheophytin-a in PDT. We then tested the cytotoxic effects of 9-hydroxypheophorbide-a (9-HpbD-a) in vitro. The cultured SNU-I041 cells were treated with serial concentrations of 9-HpbD-a followed by various energy doses (0, 0.1, 0.5, 3.2 J/$cm^{2}$) and by various interval times (0, 3, 6, 9, 12 hr) until laser irradiation, then MTT assay was applied to measure the relative inhibitory effects of photodynamic therapy (PDT). Optimal laser irradiation time was 30 minutes and the cytotoxic effects according to incubation time after 9-HpbD-a treatment increased until 6 hours, after which it then showed no increase. To observe the cell death mechanism after PDT, SUN-I041 cells were stained by Hoechst 33342 and propidium iodide after PDT, and observed under transmission electron microscopy (TEM). The principal mechanism of PDT at a low dose of 9-HpbD-a was apoptosis, and at a high dose of 9-HpbD-a it was necrosis. PDT effects were also observed in a xenografted nude mouse model. Group I (no 9-HpbD-a, no laser irradiation) and Group II (9-HpbD-a injection only) showed no response (4/4, 100%), and Group III (laser irradiation only) showed recurrence (1/4,25%) or no response (3/4, 75 %). Group IV (9-HpbD-a + laser irradiation) showed complete response (10/16, 62.5%), recurrence (4/16, 25%) or no response (2/16, 12.5%). Group IV showed a significant remission rate compared to other groups (p<0.05). These results suggest that 9-HpbD-a is a promising photosensitizer for the future and that further studies on biodistribution, toxicity and mechanism of action would be needed to use 9-HpbD-a as a photosensitizer in the clinical setting.

• Journal of Life Science
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• v.30 no.2
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• pp.113-121
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• 2020

Macrophages are initiators for regulating a host's defenses to eliminate pathogens and trigger tissue repair. Macrophages are classified into two types: classically (M1) activated macrophages and alternatively (M2) activated macrophages. M1-phenotype macrophages directly or indirectly kill infectious organisms and tumor cells via pro-inflammatory responses, whereas M2-phenotype macrophages remodel wounded tissue through anti-inflammatory responses. In this paper, we investigated how Phellinus linteus hot water extract passed from Diaion HP-20 resin (PLEP) regulates polarization of M1-like or M2-like macrophages in human THP-1 cells. PLEP did not have cytotoxicity at a high concentration of 300 ㎍/ml. We observed morphological alteration of the THP-1 cells, which are stimulated by PLEP, LPS/INF-γ (M1 stimulators) or IL-4/IL13 (M2 stimulators). PLEP exposure induced morphology contiguous with LPS/INF-γ. qPCR was also performed to determine whether PLEP influences M1 or M2 polarization-related genes. M1-phenotype macrophage-specific genes, such as TNF-α, IL-1β, IL-6, IL-8, CXCL10 and CCR7, were enhanced by PLEP in a dose-dependent manner similar to LPS/INF-γ. Conversely, M2-phenotype-specific genes, such as MRC-1, DC-SIGN, CCL17 and CCL22, were suppressed by PLEP. PLEP also significantly up-regulated secretory inflammation cytokines related to M1 polarization of macrophages, including TNFα, IL-1β and IL-6, which was similar to the gene expression. Further, MAPK and NF-κB signaling were increased by treatment with PLEP, resulting in enhancement of cytokine secretion. PLEP might therefore be used as a promising booster of pro-inflammatory responses through M1 polarization of human THP-1 cells.

• Journal of Trauma and Injury
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• v.23 no.2
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• pp.134-141
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• 2010

Purpose: A classic approach to abdominal stab wounds has been a routine laparotomy for the purpose of diagnosis or treatment. However, management protocols for abdominal stab wounds are still contentious in most trauma centers. We examined the relationship between the character of the stab wound and the injured intraabdominal organs by retrospectively analyzing the medical records of patients with abdominal stab wounds admitted to Gil hospital, and the findings for our patients are then confronted with a review of the literature. We aimed to propose proper management protocols to approach abdominal stab wounds. Methods: The medical records of all 80 patients sustaining abdominal stab wounds, admitted at the Department of Surgery, Gil Hospital, Gachon Medical School, from January 2004 to December 2008 were retrospectively reviewed. All the abdominal stab wounds were collated based on the site and the character of the injury, investigations performed on admission, results of investigations, operations performed and findings at the time of the operation. Results: The most prevalent age group was patients in their forties and the average age of the patients was 41 years for both genders. The stab wounds were most commonly located at the periumbilical area (16.9%), followed by the epigastric area (15.6%), and 18.2% of the patients had multiple wounds. The most commonly eviscerated organ was the omentum (9 out of 16 cases); 61.7% of non-eviscerated patients underwent a therapeutic laparotomy while 81.3% of eviscerated patients underwent a therapeutic laparotomy. The small bowel was the most commonly injured organ (22.7%, 17 out of 75 injuries). The review revealed a relatively common diaphragmatic injury in abdominal stab wound patients (8 cases, 10.5%). The average hospital stay was 11 days. Conclusion: This review revealed commonly eviscerated and injured intraabdominal organs in abdominal stab wound patients and their relationship with a therapeutic laparotomy. Although the management is still controversial, the authors suggest indications for an immediate laparotomy and a protocol for managing abdominal stab wounds. Hemodynamic instability and peritoneal irritation signs are definite indicators for an immediate laparotomy, but the review revealed intraabdominal organ evisceration alone not to be a statistically significant factor. In addition, the authors suggest that abnormal CT findings can be valuable for making a decision on management of hemodynamically stable stab wound patients. Further study may clarify a role for a more selective approach to operative intervention and for a more extensive use of selective observation.

• Journal of Trauma and Injury
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• v.23 no.2
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• pp.107-112
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• 2010

Purpose: Recently, the change to a more complex social structure has led to an increased frequency of traumas due to violence, accident and so on. In addition, the severity of the traumas and the frequency of penetrating injuries have also increased. Traumas to cervical and abdominal areas, what are commonly seen by general surgeons, can have mild to fatal consequences because in these areas, various organs that are vital to sustaining life are located. The exact location and characteristics of the injury are vital to treating patients with the trauma to these areas. Thus, with this background in mind, we studied, compared, and analyzed clinical manifestations of patients who were admitted to Wonju Christian hospital for penetrating injuries inflicted by themselves or others. Methods: We selected and performed a retrospective study of 64 patients who had been admitted to Wonju Christian Hospital from January 2005 to December 2009 and who had cervical or abdominal penetrating injuries clearly inflicted by themselves or others. Results: There were 51 male (79.7%) and 13 female (20.3%) patients, and the number of male patients was more dominant in this study, having a sex ratio of 3.9 to 1. The range of ages was between 20 and 86 years, and mean age was 43.2 years. There were 5 self-inflicted cervical injuries, and 19 self-inflicted abdominal injuries, making the total number of self-inflicted injury 24. Cervical and abdominal injuries caused by others were found in 11 and 29 patients, respectively. The most common area involved in self-inflicted injuries to the abdomen was the epigastric area, nine cases, and the right-side zone II was the most commonly involved area. On the other hand, in injuries inflicted by others, the left upper quadrant of the abdomen was the most common site of the injury, 14 cases. In the neck, the left-side zone II was the most injured site. In cases of self-inflicted neck injury, jugular vein damage and cervical muscle damage without deep organ injury were observed in two cases each, making them the most common. In cases with abdominal injuries, seven cases had limited abdominal wall injury, making it the most common injury. The most common deep organ injury was small bowel wounds, five cases. In patients with injuries caused by others, six had cervical muscle damage, making it the most common injury found in that area. In the abdomen, small bowel injury was found to be the most common injury, being evidenced in 13 cases. In self-inflicted injuries, a statistical analysis discovered that the total duration of admission and the number of patients admitted to the intensive care unit were significantly shorter and smaller, retrospectively, than in the patient group that had injuries caused by others. No statistically significant difference was found when the injury sequels were compared between the self-inflicted-injury and the injury-inflicted-by-others groups. Conclusion: This study revealed that, in self-inflicted abdominal injuries, injuries limited to the abdominal wall were found to be the most common, and in injuries to the cervical area inflicted by others, injuries restricted to the cervical muscle were found to be the most common. As a whole, the total duration of admission and the ICU admission time were significantly shorter in cases of self-inflicted injury. Especially, in cases of self inflicted injuries, abdominal injuries generally had a limited degree of injury. Thus, in our consideration, accurate injury assessment and an ideal treatment plan are necessary to treat these patients, and minimally invasive equipment, such as laparoscope, should be used. Also, further studies that persistently utilize aggressive surgical observations, such as abdominal ultrasound and computed tomography, for patients with penetrating injuries are needed.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.321-329
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• 1997

Purpose : It is well known that the risk of lymph nodes metastases to head and neck cancers are influenced by the location and size of the Primary tumor. as well as the degree and types of histological differentiation. However, data on the statistical analyses of lymph node metastases from the head and neck cancers among Korean Population are not available at present. In order to obtain current status of such data, we have analyzed cancer patients at the department of radiation oncology, korea universityhospital for radiation treatment. Materials and Methods : We have evaluated nine-hundred and ninetyseven (997) head and neck cancer Patients who visited to the Department of radiation oncology, between November 1981 to December 1995. After careful physical examinations and CAT scan, Patients were divided into two groups, those with positive lymph node metastases and with negative lymph node metastases. The nodal status were classified according to the TNM system of American Joint Committee on Cancer (AJCC) Besults : Four-hundred and sixteen Patients out of the 997 patients were lymph node positive $(42\%)$ and 581 patients were lymph node negative $(58\%)$ when they were first presented at the department of radiation oncelogy. According to the AJCC classification, the distribution of positive lymph node is as follow: Nl:106 $(25.5\%),\;N2a:100\;(24\%),\;N2b:68\;(16.4\%),\;N2c:69\;(16.6\%),\;3:73\;(15\%).$ respectively. The frequency of lymph node metastases according to the primary sites is as follow : larynx 283 $(28.5\%)$, paranasal sinuses: 182 $(18\%),\;oropharynx:144\;(14.5\%)\;nasopharynx:122(12\%),\;oral\;cavity\;92\;(9\%),\;hypopharynx:71\;(7\%),\;falivary\;gland:58\;(6\%)$ unknown primary:31 $(3\%),\;skin:\;14(2\%)$,. The most frequent Primary site for the positive Iymph node metastases was nasopharynx $(71\%)$ followed by hypopharynx $(69\%),\;oropharynx\;(64\%),\;oral\;cavity\;(39\%)$ The most common histologic type was squamous cell carcinoma (652/997: $65.4\%$). followed by malignant lymphoma $(109/997:11\%)$. Conclusion : Statistical results of lymph node metastases from head and neck cancer at our department were very similar to those obtained from other countries. It is concluded that the location of Primary cancer influences sites of metastases on head and neck, and stage of the primary cancer also influences the development of metastatic lesions. Since the present study is limited on the data collected from one institute. further statistical analyses on Korean cancer Patients are warrented.

• Toxicological Research
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• v.33 no.2
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• pp.107-118
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• 2017

Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration ($IC_{50}$) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.

• Neonatal Medicine
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• v.17 no.1
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• pp.21-33
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• 2010

Purpose : The increased survival of preterm infants in the neonatal intensive care unit recently has resulted in an increased frequency of bronchopulmonary dysplasia (BPD), especially with atypical forms. However, there have been few studies compairing classic and atypical BPD. The aim of this study was to investigate the differences between these two types of BPD. Methods : Infants with a gestational age less than 32 weeks born at the Seoul National University Hospital and Bundang Seoul National University Hospital from May 2004 to April 2007 were included. The data were categorized in 2 groups, classic and atypical BPD. We determined the incidence of BPD, and compared perinatal factors and postnatal managements between two groups. Results : Among 260 study subjects, 141 (54.2%) infants had BPD. Classic BPD infants were 64 and atypical BPD infants were 77. Comparison of differences between 2 groups, classic BPD infants were associated with respiratory distress syndrome, patent ductus arteriosus, intrauterine growth restriction, more high-frequency ventilator (HFV) use, low 1 and 5 minute Apgar scores. Atypical BPD infants were associated with antenatal steroid use, maternal premature rupture of membrane and chorioamnionitis (CAM). In multivariate analysis, more HFV use was associated with classic BPD. Antenatal steroid use, clinical CAM and histological CAM were associated with atypical BPD. Conclusion : The results of this study showed that antenatal factors (antenatal steroid use, clinical CAM, histological CAM) were associated with atypical BPD and postnatal factors (HFV used more) were associated with classic BPD. Further studies are needed for prevention and treatment of BPD.

• Neonatal Medicine
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• v.17 no.1
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• pp.102-108
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• 2010

Purpose : The goal of this study was to measure bilirubin levels over 6 hours using a transcutaneous bilirubinometer. The change in the bilirubin levels were recorded in anomogram. The natural progress of jaundice in neonates was monitored using the nomogram and cases were identified that needed further follow-up observation and treatment. Methods : The subjects of this study were 986 healthy term or near-term infants at the age of 35 weeks or older who were born at Sung-Ae General Hospital during the period from October 1, 2007 to April 30, 2009 and whose parents were both Koreans. Transcutaneous bilirubin measurements were obtained using a transcutaneous bilirubinometer (Minolta, JM-103) from 6 hours of life to discharge at intervals of 6 hours. A nomogram was derived from the obtained data and compared to the delivery method, gestational age, and feeding method. Results : Percentile graphs were drawn according to time. Based on the graphs, phototherapy was necessary in more than 90 percent of the infants between 35 and 37.6 weeks of age and in 95 percent of the infants 38 weeks and older. The mean bilirubin level at 24, 48, 72 and 96 hours after birth were compared according to the delivery method, gestational age, and feeding method. The bilirubin level in 48 hours was significantly higher in neonates born via cesarean section delivery compared to the neonates born via vaginal delivery, however the levels were not statistically different at the other hours. Conclusion : The results of this study show the nomogram derived from hour-specific transcutaneous bilirubin levels. This information can be used to predict the risk for subsequent significant hyperbilirubinemia.

• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.476-483
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• 1996

Following radiation therapy for brain tumors, patients often have clinical deterioration due to either radiation necrosis or recurrent tumor progression in the treatment field. The distinction between these entities is important but difficult clinically or even with CT or MRI. T1-201 has been known to accumulate in various tumors and be useful to grade, predict prognosis or detect recurrence of glioma. The aim of this study was to evaluate the usefulness of T1-201 SPECT in the differentiation of recurrent tumor from radiation necrosis. Of 67 patients who did T1-201 brain SPECT imaging with clinically suspected recurrent tumor or radiation necrosis, 20 patients underwent histopathological examination and constituted the study population. T1-201 uptake indices on T1-201 brain SPECT imaging rrere calculated and correlated with histopathological diagnosis. Of 20 patients, 15 were histopathologically confirmed as recurrent original tumor or malignant transformation of benign tumor and 5 were diagnosed as radiation necrosis. On T1-201 SPECT, 18 of 20 had T1-201 index above 2.5 which was regarded as positive indicator for the presence of tumor. Seventeen cases showed concordance, which consisted of 15 true positive and 2 true negative. Discordant 3 cases were all false positive. There was no case of false negative. The sensitivity, specificity, positive and negative predictive value of T1-201 SPECT were 100%, 40%, 83% and 100%. In conclusion, T1-201 brain SPECT is a sensitive diagnostic test in the detection of recurrent tumor following radiation therapy and is useful in the differentiation of recurrent tumor from radiation necrosis. Relatively low specificity should be evaluated further in larger number of patients in consideration of sampling error and referral bias for pathologic examination.

• Food Science of Animal Resources
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• v.28 no.1
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• pp.69-75
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• 2008

This study evaluated the physicochemical and sensory characteristics of vanilla ice cream treated with gamma irradiation. The general composition of the vanilla ice cream used for the study was 45.4-53.3% moisture, 5.5-5.9% fat and 3.9-4.1% protein, and these values did not change following gamma irradiation. The Hunter L, a and b values were slightly decreased following gamma irradiation. The fatty acid composition of the ice cream included caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid and stearic acid, and there was no detectable change following irradiation. There was no significant difference in TBARS (2-thiobarbituric acid reactive substances) values between non-irradiated and irradiated samples at a dose of 3 kGy or less (p<0.05). Sensory evaluation indicated that gamma-irradiated vanilla ice cream did not show any difference in color relative to non-irradiated ice cream. However, gamma irradiation did affect the flavor, taste and overall acceptability of ice cream at doses above 3 kGy. These results indicate that gamma irradiation at 3 kGy is an effective treatment for sustaining the physicochemical characteristics of vanilla ice cream with minimal changes in sensory characteristics, though further studies should be carried out to reduce the deterioration of sensory qualities induced by gamma irradiation.