• Korean Journal of Veterinary Research
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• v.31 no.4
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• pp.367-379
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• 1991

The purpose of this study was to investigate the effect of antioxidants (vitamin E, selenium, and coenzyme $Q_{10}$) on the bleomycin-induced pulmonary lesions in male rats. Sprague-Dawley male rats were divided into 4 treatment groups ($T_1$, $T_2$, $T_3$, $T_4$) and 4 control groups ($C_1$, $C_1$, $C_3$, $C_4$). The treatment groups of rats weie given a single intratracheal dose of bleomycin (1.5 units/rat) and control groups of rats were given a single intratracheal dose of normal saline (0.15ml/rat). The rats in the $T_1$ group and $C_1$, group were dosed with normal saline (0.5ml/kg/day), the rats in the $T_2$ group and $C_2$ group were dosed with vitamin E (50mg/kg/day), the rats in the $T_3$ group and $C_3$ group were dosed with sodium selenite (3mg/kg/day) and the rats in the $T_4$ gronp and $C_4$ group were dosed with coenzyme $Q_{10}$ (2.5mg/kg/day) intraperitoneally for 7 days or 14 days, respectively. Animals were killed at 7th and 14th day after dosing with bleomycin or saline. The results obtained were as follows: 1. Lung wet weight of treatment groups of rats was increased significantly while body weight gain of them was decreased significantly in comparison with that of control groups of rats (p<0.01). 2. The ratio(%) of lung wet weight to final body weight of treatment groups of rats was increased significantly in comparison with that of control groups of rats (p<0.01). 3. The main histopathological findings of lungs observed in rats at 7th day after dosing with bleomycin were proliferation of the type II alveolar epithelial cells and fibroblasts, increased invading of macrophages into lesions, round cell infiltration and perivascular edema. 4. Lung fibrous tissues were markedly increased in rats observed at 14th day after dosing with bleomycin. 5. Pumonary lesions observed in rats dosed with bleomycin and antioxidants(vitamin E, selenium, coenzyme $Q_{10}$) were not significantly different from those of rats given bleomycin alone.

• Journal of Korean Medical Science
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• v.33 no.52
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• pp.336.1-336.12
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• 2018

Background: We aimed to investigate mucosal immunity related to forkhead box P3 ($FOXP3^+$) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods: Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-$ROR{\gamma}t$ antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin $(IL)-1{\beta}$, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon $(IFN)-{\gamma}$, soluble CD40L, and tumor necrosis factor-${\alpha}$. Results: $FOXP3^+$ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. $ROR{\gamma}t^+$ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 ($9.6{\pm}1.5$ vs. $12.7{\pm}3.0$), IL-21 ($14.9{\pm}1.5$ vs. $26.4{\pm}9.1$), IL-33 ($14.3{\pm}0.9$ vs. $19.1{\pm}5.3$), and $IFN-{\gamma}$ ($15.2{\pm}5.9$ vs. $50.2{\pm}42.4$) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 ($119.1{\pm}79.6$ vs. $52.9{\pm}39.1$) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A ($64.2{\pm}17.2$ vs. $28.3{\pm}10.0$) and IL-22 ($37.5{\pm}8.8$ vs. $27.2{\pm}3.7$) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion: Mucosal immunity analysis showed increased $FOXP3^+$ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.3
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• pp.134-149
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• 2016

Objectives : Gal-Geun-Tang (GT) has been described from SANGHAN in Korean traditional medicine and known to act against cold, fever, hypertension, and nasal catarrh. However, little has yet been learned about the effect of GT on immune function. In the current study, in vitro and in vivo immunomodulatory activity of GT (water extract) was investigated.Methods : Water extract of GT induced in vitro proliferation of spleen cells and significantly increased their proliferative responses during anti-CD3 activation. Using purified splenic T and B cells, it was revealed that GT has a mitogenic activity to B cells and promotes their proliferation induced by lipopolysaccharide, whereas T cell proliferation was not triggered and GT was rather inhibitory to T cell activation caused by anti-CD3 antibody. In the presence of antigen presenting cells (APC), GT addition resulted in a significant increase of IFNγ and IL-4, but not IL-2, production. However, addition of high concentration (1,000㎍/㎖) of GT led to a marked reduction in T cell cytokine production and under such condition, GT facilitated apoptosis of T cells when examined by flow cytometry with propidium iodide staining.Results : In vivo immunomdulation of GT was also investigated using a mouse model. Following keyhole limpet hemocyanin (KLH) immunization, GT (1 ㎎/day) was orally administered for 9 days. Cell numbers in thymus, spleen and peripheral blood were not altered by GT administration, indicating that such dose is not immunotoxic. Cell numbers in draining lymph nodes (LN) and ex vivo Ag-specific proliferation of LN cells were significantly elevated by GT administration. However, any preferential stimulation of T or B and CD4⁺ or CD8⁺ T cell subpopulations was not observed in a flow cytometric analysis of LN cells. This result shows that GT does not promote in vivo B cell proliferation while GT enhances Ag-specific proliferation of LN cells, unlike what was observed in vitro.Conclusions : For a further understanding of in vivo immunomodulatory activity of GT, ex vivo cytokine production of LN cells obtained from KLH-immunized mice was evaluated. Ag-specific IFNγ production was significantly higher in GT-treated mice when compared to PBS-treated control mice. In contrast, IL-4 production in GT-treated group was comparable to control group unlike to in vitro data. In addition, GT administration did not result in any significant differences in serum levels of Ig (IgM, IgG1 and IgG2a) between GT-treated and control groups. Taken together, these data strongly support that GT promotes immune response, more profoundly type 1 helper T cell (Th1) activity and GT may be applicable for treatment of intracellular parasite infection such as viral diseases.

• Korean Journal of Animal Reproduction
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• v.18 no.4
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• pp.235-244
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• 1995

The present study was designed to demonstrate that ES cell lines efficiently could be isolated from explanted blastocysts of hybrid BCF1 mouse when grown on STO feeder layer derived from mouse fibroblasts in culture medium supplemented with leukemia inhibitory factor (LIF). The expanded blastocysts were attached to mitomycin C-inactivated STO feeder layer and were cultured for 4 days. Four days later the ICM was disaggregated by a short term trypsin treatment (0.25% trypsin / 0.04% EDT A for 2-3 min). The resulting cell suspension was seeded on a new STO feeder layer and covered with DMEM supplemented with 10% FCS, 0.1 mM nonessential amino acid, 0.1 mM sodium pyruvate, 0.1 mM mercaptoethanol and 1,000 U/ml LIF. Colonies of ES-like cells were observed after the second passage. These colonies were repeatedly passaged at approximately 5 day intervals. In this study, five ES-like celllines were isolated by directly explanting blastocysts, but three lines were lost after the 5th passage, possibly due to toxic effects of a new FCS batch. The characterization of developmental potential of isolated cell lines was performed with respect to in vitro differentiation and specific activity of alkaline phosphatase (AP). When cells were cultured in suspension, the aggregates of cell lines were capable of forming simple embryoid bodies (EB), and showed the capacity for forming cystic multilayer EBs. In addition, the cell lines were positive for AP staining, a biochemical marker characteristic of mouse ES cells.

• Molecules and Cells
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• v.45 no.11
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• pp.833-845
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• 2022

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as Gata3 and Tcf7. Finally, regarding lung macrophages, hUC-MSCs reduced the total number of macrophages, particularly the proportion of the enhanced monocyte-derived macrophage population. In a closer examination of monocyte-derived macrophages, hUC-MSCs reduced the M2a and M2c populations. In conclusion, hUC-MSCs can be considered as a potential anti-asthmatic treatment given their therapeutic effect on the asthmatic airway inflammation in a murine asthma model by modulating innate immune cells, such as ILC2s, M2a, and M2c macrophages, as well as affecting Tregs and effector T cells.

• Journal of Chest Surgery
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• v.12 no.4
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• pp.324-335
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• 1979

During the period of 4 years from August 1975 to August 1979 one hundred and forty seven cases of lung cancer were seen at Paik Foundation Hospital in Seoul, Korea. Among these 147 cases, 104 patients had primary carcinoma of the lung and the remainder was metastatic carcinoma to the lung. Among these 104 primary carcinoma patients, 73 cases were proven histologically as primary carcinoma of the lung. There were three cases of alveolar cell carcinoma [Table 1 ]. This clinical observation is based on those 73 cases including three case reports of the alveolar cell carcinoma. 1. Peak incidence was observed in the 5th decade of life. Male to female ratio was 2 to 1 [Fig. 1]. 2. Pathological classifications were as follows: epidermoid carcinoma, 24 cases [32.9%]; undifferentiated carcinoma, 20 cases [27.4%]; adenocarcinoma, 15 cases [20.5%]; bronchioloalveolar carcinoma [5.5%] and positive cytology, 10 cases [13.7%] [Fig. 2]. 3. Evidence of inoperability was observed in 55 patients [75% of the 73 cases] [Table 3]. 4. Among those 73 cases, operability was evaluated in 18 patients or 25%. One patient refused operation and 17 patients [23.6%] were explored. In 11 [15%] out of 17 patients, thoracotomies were performed. Six cases were pneumonectomies and 5 cases were lobectomies or bilobectomies [Fig. 3]. 5. First case of alveolar cell carcinoma was a 46 year-old housewife complaining of cough and hemoptysis for one year. The plain chest X-ray and bronchogram showed characteristic pictures as Figures 4 and 5. A pneumonectomy was carried out. Histologically, a beautiful alveolar carcinoma consisted of the characteristic tall columnar epithelial cells, which were lining the alveolar spaces as seen in Figures 6, 7, 8, and 20. 6. In the second case of 41 year old male, predominant clinical feature was single, well defined mass in the right lower lobe [Fig. 10 and 11] on chest X-ray. Bilobectomized specimen showed fragile, soft and hard tissue containing mucoid secretions and focal yellowish necrosis with pigmentation on cut surface [Fig. 12]. Slides showed tumor cells lined up along the alveolar septa with papillary projections [Fig. 13 and 14]. 7. Third case of alveolar cell carcinoma was a 50-year-old housewife with hemoptysis. An outstanding clinical picture was a round to lobulated mass in the right upper lobe [Fig. 16]. She is living now, 2 years and 1 month post-operatively, but has arrived at terminal stage with military nodular disseminations to the contralateral lung [Fig. 19].

• Journal of Chest Surgery
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• v.29 no.1
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• pp.43-51
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• 1996

From march 1989 to October 1993, 57 patients were diagnosed and operated for primary non-small cell lung cancer, and evaluated clinically. 1. There were 45 males and 12 females (M:F=3.8:1), and the peak incidence of age was 6th decade of life (45.6%). In the preoperative diagnostic methods and their positive rate, sputum cytology was 11%, bronchial washing cytology 50%, bronchoscopic biopsy 73%, and CT guided percutaneous needle aspiration biopsy 83%. 3. Histopathologically, squamous cell carcinoma was 56.1%, adenocarcinoma 22.8%, bronchioloal veolar cell carcinoma 1%, and undifferentiated large cell carcinoma 1.8%. 4. In the operation, pneumonectomy was 35.1%, lobectomy 38.6%, bilobectomy 3.5%, segmentec tony 7%, and exploratory thoracotomy 15.8%, and overall resectability was 84.2%. 5. In postoperative stagings, stage I was 28.1%, st ge II 22.8%, stage IIIa 31.6% and stage IIIb 17.5%. 6. Postoperative complications were developed in 11 cases (19.3%) and operative mortality was none. 7. One year survival rate in rejectable cases was 87.0%, 2 year 61.6% and 5 year 44.9%. According to stage, 3 year survival rate was 75.8% in stage I, 16.9% in stage II, 60.9% in stage IIIa, 50% in stage IIIb.

• Development and Reproduction
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• v.6 no.2
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• pp.117-122
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• 2002

Dopamine(DA), norepinephrine(NE), and epinephrine(E) belong to a class of neurotransmitters known as catecholamine (CA) which are synthesized and secreted by mammalian brain and adrenal medulla. CA regulate several behavior patterns connected with breeding, and regulate GnRH-gonadotropin hormone axis' vitality between hypothalamus-pituitary gland linking with reproduction freeze. The present study examined effects of sex steroid hormone on the transcriptional activities of CA biosynthesis enzymes, tyrosine hydroxylase(TH), dopamine $\beta$ -hydroxylase(DBH), and phenylethaolamine-N-methyl transferase(PNMT). Mature female rats were ovariectomized(OVX) and implanted with 17 $\beta$-estradiol(E$_2$: 500 $\mu\textrm{g}$/ml) or sesame oil. Forty-eight hours after implantation all the animals were sacrificed. Total RNAs were extracted immediately and were applied to semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR). The expression level of TH was appeared by hypothalamus > SNc> adrenal medulla orders in OVX＋Oil group, and by SNc > hypothalamus) adrenal medulla orders in OVX+E$_2$ group. Treatment with E$_2$ significantly increased TH expression in SNc and adrenal medulla but in hypothalamus, the reduced TH expression was observed. The expression level of DBH was appeared by adrenal medulla > SNc > hypothalamus orders in OVX＋Oil group and in OVX＋E$_2$ group. Administration of E$_2$ significantly reduced DBH expression in SNc, and increased in adrenal medulla. Two cDNA products, large(PNMT1) and small(PMNTs) species of 110bp difference, were amplified in SNc and hypothalamus, but only PNMTs was observed in adenal medulla. The PNMTs expression level was in the order of adrenal medulla > hypothalamus > SNc in both OVX＋Oil and OVX＋E$_2$ group. The PNMTs expression in SNc and adrenal medulla was significantly increased byE$_2$. The present report demonstrated that estrogen effects on transcriptional activities for CA biosynthethic enzymes were tissue specific in adrenal medulla as well as different region of brain. These results suggest that it might be crucial relationship between the type of estrogen receptor and CA enzyme gene expression.

• Journal of Korean Neurosurgical Society
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• v.59 no.2
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• pp.106-116
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• 2016

Objective : Protein disulfide isomerase (PDI) acts as a chaperone on the cell surface, and it has been reported that PDI is associated with the tumor cell migration and invasion. The aims of this study are to investigate the anti-migration effect of bacitracin, which is an inhibitor of PDI, and the associated factor in this process. Methods : U87-MG glioma cells were treated with bacitracin in 1.25, 2.5, 3.75, and 5.0 mM concentrations. Western blot with caspase-3 was applied to evaluate the cytotoxicity of bacitracin. Adhesion, morphology, migration assays, and organotypic brain-slice culture were performed to evaluate the effect of bacitracin to the tumor cell. Western blot, PCR, and gelatin zymography were performed to investigate the associated factors. Thirty glioma tissues were collected following immunohistochemistry and Western blot. Results : Bacitracin showed a cytotoxicity in 3rd (p<0.05) and 4th (p<0.001) days, in 5.0 Mm concentration. The cell adhesion significantly decreased and the cells became a round shape after treated with bacitracin. The migration ability, the expression of phosphorylated focal adhesion kinase (p-FAK) and matrix metalloproteinase-2 (MMP-2) decreased in a bacitracin dose- and time-dependent manner. The U87-MG cells exhibited low-invasiveness in the 2.5 mM, compared with the untreated in organotypic brain-slice culture. PDI was expressed in the tumor margin, and significantly increased with histological glioma grades (p<0.001). Conclusion : Bacitracin, as a functional inhibitor of PDI, decreased the phosphorylated FAK and the secreted MMP-2, which are the downstream of integrin and play a major role in cell migration and invasion, might become one of the feasible therapeutic strategies for glioblastoma.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.124-124
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• 2003

The successful development of embryos cloned by nuclear transfer (NT)have been dependent on a wide range of known factors including cell cycle of donor and recipient ooplast, oocyte quality, NT procedure and oocyte activation. The present study compared the development of cloned porcine embryos following different activation treatments. Cumulus-oocyte complexes (COCs) were aspirated from 26 mm follicles of slaughterhouse ovaries and cultured for 22 h in NCSU #23 medium supplemented with 10% porcine follicular fluid, 0.57 mM cysteine, 0.5 g/mL LH, 0.5 g/mL FSH and 10 ng/mL EGF. The COCs were further cultured for an additional 22 h in the same medium at $39{\cird}C$ in an atmosphere of 5% $CO_2$ in air, without hormonal supplements. Primary cultures of fibroblasts isolated from a female fetus on day 40 of gestation were established in DMEM + 15% FCS. For nuclear donation, cells at the 5th-6th passage were cultured in DMEM +0.5% FCS for 5 days in order to arrest the cells in G0/Gl. After enucleation, oocytes were reconstructed by transfer of donor cells and fusion with three DC pulses (1.4 KV/cm, 30 sec) in 0.28 M mannitol containing 0.01 mM $CaCl_2$ and 0.01 mM $MgCl_2$. Eggs were then divided into three treatment groups, control (without further treatment, Group 1), eggs cultured in 10 g/ml cycloheximide (CHX) for 5 h (Group 2), and eggs cultured in 1.9 mM 6-dimethylaminopurine (6-DMAP) for 5 h (Group 3). The eggs were then cultured in sets of 30 in 60 I drops of NCSU#23 supplemented with 4mg/ml BSA (essentially fatty acid free) until day 7 at $39{\circ}C$ in a humidified atmosphere of 5% $CO_2$. On day 4 the culture were fed by adding 20 I NCSU #23 supplemented with 10% FBS. Development rates into blastocysts were significantly higher (P<0.05) in Group 3 embryos compared to Group 1 controls ($27.6 \mu 2.7% vs. 20.1 \mu 4.1%$, respectively), but rates did not differ in Group 2 compared to control ($23.8 \mu 5.7%$). Total cell number in Group 3 blastocysts was however significantly higher (P<0.05) than in Groups 1 and 2 ($44.6 \mu 2.4 vs. 19.9 \mu 1.9 and 21.9 \mu 2.1$, respectively). These results suggest that 6-DMAP is more efficient than cycloheximide in the activation of electrically fused NT oocytes during in vitro production of cloned porcine embryos.