• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.166-172
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• 2000

Prior to a clinical trial, the in vitro and in vivo antitumor effects of a new recombinant human interferon ${\alpha}-2a$ (rHu/IFN ${\alpha}-2a$) with/without hydroxyurea (HU) were investigated using chronic myelogenous leukemia (CML)-derived cell lines (K562 and KU812F) and BALB/c nude. mice transplanted with KU812F cells. The rHu/IFN ${\alpha}-2a$ ($10^4-10^6IU/ml$) strongly inhibited proliferation of both cell lines and the combined treatments with HU ($10{\mu}g/ml$) were more effective. In nude mice transplanted with KU812F cells. rHu/IFN ${\alpha}-2a(1{\times}10^6IU$) inhibited tumor growth by 42-65% at 15-21 days post-transplantation (DPT). The combined treatment of rHu/IFN ${\alpha}-2a (5{\times}10^5IU$) with HU (0.25mg/g b.w.) inhibited the tumor growth by 48-67% at 12-21 DPT. In addition, the treatment of rHu/IFN ${\alpha}-2a$ ($5{\times}10^6IU\;or\;1{\times}10^7IU$) rejected tumor transplantation by 40%. These results suggest that the new rHU/IFN ${\alpha}-2a$ alone or with HU is effective on CML cell lines.

• Journal of Pharmaceutical Investigation
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• v.16 no.3
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• pp.118-123
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• 1986

Time-concentration curves of recombinant human interferon alpha$(rIFN-{\alpha}A)$ in the skin and serum of nude mice or rats were studied after topical application of IFN ointment. IFN appeared in the skin and serum in less than 30 minutes and lasted for more than 10-12 hours at high concentration level after the application to nude mice at a dose of $9.0{\times}10^5\;IU/g$ mouse. But in the rats, IFN was not detected in the serum even 7 hours after the application at a dose of $6.0{\times}10^5\;IU/g$ rat. Topical application of IFN might be useful for the topical and systemic treatment if the human skin resembles that of nude mouse in respect to transport characteristics.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.497-505
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• 2002

Background : INF-${\gamma}$ plays an important role in the host response to a mycobacterial infection. A complete IFN-${\gamma}$ receptor 1 deficiency is a life threatening condition because it renders patients highly susceptible to a mycobacterial infection. Several mutations in the IFN-${\gamma}$ receptor and STAT1 gene have been identified in the rare mycobacterial infections. These mutations have partial function of the IFN-${\gamma}$ receptor and similar pathologic features to clinical tuberculosis. Materials and Methods : The function of the IFN-${\gamma}$ receptor was evaluated in the patients with clinical tuberculosis. In addition, the DNA coding sequence of the IFNgR1 and STAT1 gene was also analyzed in disseminated tuberculosis patients who might have a defective IFN-${\gamma}$ receptor. Results : The cell surface expression levels of HLA-DR and CD64 in the PMBC after being stimulation with IFN-${\gamma}$ (100IU/ml, 1000IU/ml) were increased in both controls and patients. However, the rate of increase in both groups was similar. The production of TNF-${\alpha}$ in the response to stimulation with LPS was higher in the both groups ($850.7{\pm}687.8$ vs. $836.7{\pm}564.3$ pg/ml). Pretreatment with IFN-${\gamma}$ prior to LPS stimulation resulted in further increase in TNF-${\alpha}$ production between both groups ($2203.5{\pm}242.5$ vs. $2227.5{\pm}560.4$ pg/ml). However, the rate of the increase in TNF-${\alpha}$ production in the both groups was similar. The known mutations in the IFNgR1 and STAT1 coding sequences were not found in the genomic DNA of patients with disseminated tuberculosis. Conclusion : The functional and genetic defects of the IFN-${\gamma}$ receptor were not identified in clinical tuberculosis. This suggests the defective IFN-${\gamma}$ receptor that predispoe patients to a BCG or NTM infection can not alone account for the cases of clinical tuberculosis.

• Journal of Life Science
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• v.5 no.2
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• pp.81-89
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• 1995

The antitumor activities of the cell bound polysaccharide(CBP), water soluble polysaccharide(WSP) and sulfated polysaccharide(SP) of Zoogloea sp. were observe. The results obtained were as follows : 1) The CBP, WSP, and SP showed cytotoxic effect on the Meth A cells in vitro, however, the effect of CBP and WSP was more ten-fold greater than that pf SP. 2) When CBP, WSP, and SP was inoculated into the peritoneal cavity of the Meth A cells transplanted mice, the average survival days tended to prolonged slightly as compared with the control. 3) When Meth A cells were transplanted subcutaneously into the back side of mice, and then CBP, WSP, and Sp was inoculated into the peritoneal cavity of mice, the tumor growth inhibition ratio was 46.9% for WSP, 40.4% for CBP, and 16.2% for SP. 4) The phagocytic activity of peritoneal macrophages elicited with CBP, WSP, and SP was significantly increased than that of control. 5) The production of nitric oxide in the peritoneal macrophages stimulated with CBP, WSP, SP, and LPS aloneo was not increased than that of control. The production of nitric oxide in the peritoneal macrophages stimulated with IFN-r and CBP, IFN-r and WSP and IFN-r and SP was significantly increased than that of control, but in the case of stimulated with IFN-r and WSP was increased 50% for CBP and SP. These results suggest that the CBP, WSP and SP of Zoogloea sp. showed direct cytotoxic effect and tumor growth inhibition on Meth A cells in vitro and in vivo, and induced nitric oxide production of activated macrophages.

• Tuberculosis and Respiratory Diseases
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• v.55 no.3
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• pp.250-256
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• 2003

Background : Anthracofibrosis, a descriptive term for multiple black pigmentation with fibrosis on bronchoscopic examination, has a close relationship with active tuberculosis (TB). However, TB activity is determined in the later stage by the TB culture results in some cases of anthracofibrosis. Therefore, it is necessary to identify early markers of TB activity in anthracofibrosis. There have been several reports investigating the serum levels of IL-2 $sR{\alpha}$, IFN-${\gamma}$ and TBGL antibody for the evaluation of TB activity. In the present study, we tried to measure the above mentioned serologic markers for the evaluation of TB activity in patients with anthracofibrosis. Methods : Anthracofibrosis was defined when there was deep pigmentation (in more than two lobar bronchi) and fibrotic stenosis of the bronchi on bronchoscopic examination. The serum of patients with anthracofibrosis was collected and stored under refrigeration before the start of anti-TB medication. The serum of healthy volunteers (N=16), patients with active TB prior to (N=22), and after (N=13), 6 month-medication was also collected and stored. Serum IL-2 $sR{\alpha}$, IFN-${\gamma}$ were measured with ELISA kit (R&D system, USA) and serum TBGL antibody was measured with TBGL EIA kit (Kyowa Inc, Japan). Results : Serum levels of IL-2 $sR{\alpha}$ in healthy volunteers, active TB patients before and after medication, and patients with anthracofibrosis were $640{\pm}174$, $1,611{\pm}2,423$, $953{\pm}562$, and $863{\pm}401$ pg/ml, respectively. The Serum IFN-${\gamma}$ levels were 0, $8.16{\pm}17.34$, $0.70{\pm}2.53$, and $2.33{\pm}6.67$ pg/ml, and TBGL antibody levels were $0.83{\pm}0.80$, $5.91{\pm}6.71$, $6.86{\pm}6.85$, and $3.22{\pm}2.59$ U/ml, respectively. The serum level of TBGL antibody was lower than of other groups (p<0.05). There was no significant difference of serum IL-2 $sR{\alpha}$ and IFN-${\gamma}$ levels among the four groups. Conclusion : The serum levels of IL-2 $sR{\alpha}$, IFN-${\gamma}$ and TBGL antibody were not useful in the evaluation of TB activity in patients with anthracofibrosis. More useful ways need to be developed for the differentiation of active TB in patients with anthracofibrosis.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.501-505
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• 2005

Immu-Forte composed of chitosan, ${\beta}-glucan$, manno-oligosaccharide and pangamic acid was evaluated for its effectiveness as a nonspecific immunostimulator in mice. The effects of Immu-Forte were determined by analysis of cytokines using ELISA and phenotype of leukocyte subpopulations using monoclonal antibodies specific to mouse leukocyte differentiation antigens and flow cytometry. All T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, IL-2, IL-4, IL-12 and IFN-r in Immu-Forte A-treated group increased in 1 months posttreatment and were significantly higher (p < 0.05) than that of control at 1 months posttreatment. All T cells, all B cells, CD4 T cells, CD8 T cells, macrophages and IL-2 in Immu-Forte EX-treated low and middle dose groups increased in 1 months posttreatment and were significantly higher (p < 0.05) than that of control at 1 months posttreatment. In the Immu-Forte soybean-treated group, NK cells and IL-4 were significantly higher in middle dose-treated group, and IL-2, IL-4 and IFN-r were significantly higher in low dose-treated group. In the Immu-Forte F-treated group, all T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, NK cells, IL-2, IL-4, IL-12 and IFN-r in high dose-treated group and all T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, IL-2, IL-4, IL-12 and IFN-r in middle dose-treated group and NK cells, IL-2, IL-4, IL-12 and IFN-r in low dose-treated group were significantly higher (p < 0.05) than that of control at 1 months posttreatment. In conclusion, this study has demonstrated that Immu-Forte had an immunostimulatory effect on mice through proliferation and activation of mouse immune cells.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.11 no.1
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• pp.1-22
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• 1998

During the last few years, nitric oxide(NO) as a potent macrophage-derived effector molecule against a variety of bacteria, parasites, and tumors has received increasing attention. More recent studies suggest that NO also has antiviral effects in both murine and human cells. The objective of the current study was to determine the effect of Yongdamsagantang(YST) on the production of NO. Stimulation of mouse peritoneal macrophages with YST after the treatment of recombinant $interferon-{\gammer}(rlFN-{\gammer})$ resulted in the increased NO synthesis. YST had no effect on NO synthesis by itself. When YST was used in combination with $rIFN-{\gammer}$, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of YST on NO synthesis was shown 6 hour after treatment with $rIFN-{\gammer}$. This increase in NO synthesis was reflected as increased amount of inducible NO synthase(iNOS) protein. NO production was inhibited by $N^G-monomethyl-L-arginine$. The increased production of NO from $rIFN-{\gammer}$ plus YST-stimulated cells was decreased by the treatment with staurosporin. In addition, synergy between $rIFN-{\gammer}$ and YST was mainly dependent on YST-induced tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ secretion. These results suggest that the capacity of YST to increase NO production from $rIFN-{\alpha}-primed$ mouse peritoneal macrophages is the result of YST-induced $TNF-{\alpha}$ secretion.

• Toxicological Research
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• v.3 no.1
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• pp.55-63
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• 1987

A Peri-and Postnatal Study was Carried out to examine the effects of rHuIFN-${\alpha}A$, produced by gene-manipulated E. coli, on offsprings of Wistar rats. The substance was administered intraperitoneally to dams at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day during the period from day 17 of gestation to day 21 after delivery. All the pregnant dams were allowed to deliver naturally, and the postnatal development of the offsprings was observed. No noticeable toxic effects and pathological changes on dams were observed, and no detectable variations in postnatal development of offsprings occured.

• Proceedings of the Korean Society for Applied Microbiology Conference
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• 1986.12a
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• pp.520.2-520
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• 1986

Ames test와 포유동물 배양세포를 이용한 염색체 이상시험을 통하여 유전자 조작된 대장균이 생산한 알파 인터페론의 변이원성 유무를 조사하였다. rHu IFN-$\alpha$ A는 S. typhimurium (TA 1535, TA 1537, TA 1538, TA 98, TA 100) 에 30, 3000, 30,000 IU/plate의 농도에서 변이원성을 나타내지 않았으며, rat(Sprague-Dawley)의 골수세포를 이용한 생체내 염색체 이상시험을 실시하여 양성대조군인 nitroso-guanidine과 rHu IFN-$\alpha$A 각각에 대한 염색체 구조 이상의 출현율을 조사하였다.

• YAKHAK HOEJI
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• v.41 no.3
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• pp.365-369
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• 1997

Human chorionic gonadotropin (hCG) is a placental hormone and is involved in maintenance of the corpus luteum during pregnancy. In the present study, effect of hCG on nitiric ox ide (NO) generation from peritoneal macrophage was examined. hCG ahd no effect on NO generation by itself, whereas recombinant interferon- ${\gamma}$ (rIFN-${\gamma}$) alone had modest activity. When hCG was used in combination with rIFN-${\gamma}$, there was a marked cooperative induction of NO generation in a dose-dependent manner. The optimal effect of hCG on NO generation was shown at 6 hr after treatment with rIFN-${\gamma}$. Furthermore, northern blot analysis of showed that hCG increased the expression of inducible NO synthase(iNOS) gene. These results suggest that hCG induces NO generation from macrophages by increasing the expression of iNOS gene.