• Journal of Korean Neurosurgical Society
• /
• v.54 no.3
• /
• pp.225-231
• /
• 2013

Objective : Spinal dysraphism defects span wide spectrum. Wound dehiscence is a common postoperative complication, and is a challenge in the current management of cerebrospinal fluid (CSF) leaks and wound healing. The purpose of this study is to evaluate the risks of CSF-related morbidity in the surgical treatment of spinal dysraphism. Methods : Ten patients with spinal dysraphism were included in this retrospective study. The median age of the cohort was 4.8 months. To assess the risk of CSF morbidity, we measured the skin lesion area and the percentage of the skin lesion area relative to the back surface for each patient. We then analyzed the relationship between morbidity and the measured skin lesion area or related factors. Results : The overall median skin lesion area was 36.2 $cm^2$ (n=10). The percentage of the skin lesion area relative to the back surface ranged from 0.6% to 18.1%. During surgical reconstruction, 4 patients required subsequent operations to repair CSF morbidity. The comparison of the mean area of skin lesions between the CSF morbidity group and the non-CSF morbidity group was statistically significant (average volume skin lesion of $64.4{\pm}32.5cm^2$ versus $27.7{\pm}27.8cm^2$, p<0.05). CSF morbidity tended to occur either when the skin lesion area was up to 44.2 $cm^2$ or there was preexisting fibrosis before revision with an accompanying broad-based dural defect. Conclusion : Measuring the lesion area, including the skin, dura, and related surgical parameters, offers useful information for predicting wound challenges and selecting appropriate reconstructive surgery methods.

• BMB Reports
• /
• v.52 no.5
• /
• pp.336-341
• /
• 2019

The cGAS-STING pathway plays an important role in pathogen-induced activation of the innate immune response. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) found predominantly in the synovial fluid of osteoarthritis (OA) patients increases the expression of catabolic factors via the toll-like receptor-2 (TLR-2) signaling pathway. In this study, we investigated whether 29-kDa FN-f induces inflammatory responses via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway in human primary chondrocytes. The levels of cGAS and STING were elevated in OA cartilage compared with normal cartilage. Long-term treatment of chondrocytes with 29-kDa FN-f activated the cGAS/STING pathway together with the increased level of gamma-H2AX, a marker of DNA breaks. In addition, the expression of pro-inflammatory cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF-2), granulocyte colony-stimulating factor (G-CSF/CSF-3), and type I interferon ($IFN-{\alpha}$), was increased more than 100-fold in 29-kDa FN-f-treated chondrocytes. However, knockdown of cGAS and STING suppressed 29-kDa FN-f-induced expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ together with the decreased activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and inhibitor protein ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$). Furthermore, NOD2 or TLR-2 knockdown suppressed the expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ as well as decreased the activation of the cGAS/STING pathway in 29-kDa FN-f-treated chondrocytes. These data demonstrate that the cGAS/STING/TBK1/IRF3 pathway plays a critical role in 29-kDa FN-f-induced expression of pro-inflammatory cytokines.

• 한국생물공학회:학술대회논문집
• /
• 2003.10a
• /
• pp.329-333
• /
• 2003

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) is a glycoprotein that stimulates the production of granulocytes, macrophages and white blood cells. hGM-CSF secreted by transgenic Nicotiana tabacum suspension cells was unstable in the culture medium and rapidly degraded by extracellular preteases. In order to reduce extracellular pretense activity, culture temperature was lowered. Then, the production of hGM-CSF by transgenic plant suspension cell cultures could be enhanced by reduced degradation of hGM-CSF at low temperature.

• Biomolecules & Therapeutics
• /
• v.5 no.2
• /
• pp.110-116
• /
• 1997

The present study was designed to evaluate the effects of a recombinant human granulocyte-colony stimulating factor (G-CSF) on leukopenia and tumor growth in mice treated with DA-125, an adri-amycin (ADM) derivative. In normal mice, single intravenous injection of DA-125 produced transient leukopenia accompanied with weight loss and splenic atrophy in a dose-related manner. However, subcutane-ous administration of G-CSF (5$\mu$g/head) for 5 consecutive days after DA-125 resulted in a significantly elevated nadir of leukocyte counts and facilitation of recovery from the leukopenia. To investigate the effect of G-CSF on antitumor effects of DA-125, ADM (12 mg/kg) or DA-125 (40 mg/kg) was administered to Colon-26 murine adenocarcinoma-bearing Balb/c mice with G-CSF. Regardless of treatment with G-CSF, DA-125 and ADM markedly retarded the growth of implanted tumor, though they failed to increase mean survival time of tumor-bearing mice. These results suggest that G-CSF is able to not only ameliorate, but reconstitute DA-125-induced myelosuppression without affecting its antitumor potential.

• The Korea Journal of Herbology
• /
• v.28 no.5
• /
• pp.113-119
• /
• 2013

Objectives : The purpose of this study was to investigate the effects of Angelicae Gigantis Radix Water Extract(AG) on the production of proinflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide(LPS). Method : RAW 264.7 cells were cotreated with AG(50 and 100 ug/mL) and lipopolysaccharide(LPS; 1 ug/mL) for 24 hours. After 24 hour treatment, using Bead-based multiplex cytokine assay, concentrations of various cytokines such as interleukin(IL)-6, IL-$1{\beta}$, IL-10, tumor necrosis factor-alpha(TNF-${\alpha}$), granulocyte colony-stimulating factor(G-CSF), granulocyte macrophage colony-stimulating factor(GM-CSF), interferon inducible protein-10(IP-10), leukemia inhibitory factor(LIF), lipopolysaccharide-induced chemokine(LIX), monocyte chemoattractant protein-1(MCP-1), macrophage colony-stimulating factor(M-CSF), macrophage inflammatory protein(MIP)-$1{\alpha}$, MIP-$1{\beta}$, MIP-2, Regulated on Activation, Normal T cell Expressed and Secreted(RANTES) and vascular endothelial growth factor(VEGF) were measured. Result : AG significantly inhibited LPS-induced production of TNF-${\alpha}$, MIP-$1{\alpha}$, G-CSF, RANTES, IL-10, and M-CSF from LPS-stimulated RAW 264.7 cells at the concentrations of 50 and 100 ug/mL. AG significantly inhibited LPS-induced production of MIP-$1{\beta}$, MIP-2, GM-CSF, and IL-6 from LPS-stimulated RAW 264.7 cells at the concentrations of 50 ug/mL. AG significantly inhibited LPS-induced production of VEGF from LPS-stimulated RAW 264.7 cells at the concentrations of 100 ug/mL. But AG did not show any significant effect on the production of MCP-1, LIF, LIX, IP-10 and IL-$1{\beta}$ from LPS-induced RAW 264.7 cells. Conclusion : These results suggest that AG has anti-inflammatory effect related with its inhibition of proinflammatory mediators such as TNF-${\alpha}$, MIP-$1{\alpha}$, G-CSF, RANTES, IL-10, MIP-$1{\beta}$, MIP-2, GM-CSF, IL-6, VEGF and M-CSF in LPS-induced macrophages.

• Journal of Plant Biotechnology
• /
• v.31 no.2
• /
• pp.163-167
• /
• 2004

The effects of sucrose concentration on the secretion of hGM-CSF, total protein and protease into the medium were investigated in transgenic tobacco cells. The dry cell weight (11.22 g/L), hGM-CSF (181.53 $\mu\textrm{g}$/L) and total protein (66.8 mg/L) were detected as highest at 30 g/L sucrose and protease activity (2660 U/L) was highest at 120 g/L sucrose after 5-day culture. However after 10-day culture, the maximum dry cell weight (28.36 g/L) was found at 60 g/L sucrose while the maximum hGM-CSF (95 $\mu\textrm{g}$/L) was appeared at 150 g/L sucrose. The total protein and protease activity was secreted as 52.28mg/L and 3430 U/L, respectively in the same culture.

• IMMUNE NETWORK
• /
• v.6 no.1
• /
• pp.13-19
• /
• 2006

Background: Granulocyte colony stimulating factor (G-CSF) is known as a cytokine central to the hematopoiesis of blood cells and to modulate their cellular functions. Besides granulocytes and their precursors, monocytes/macrophages and endothelial cells are direct target cells of G-CSF action. G-CSF influences immune cells in an anti inflammatory way. Methods: To evaluate whether G-CSF has a potential for preventing or ameliorating diseases characterized by mucosal inflammation, we used a mouse model with trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. To the mice model G-CSF was administrated daily by intraperitoneal injection. Macroscopic evaluation and immunohistochemical analysis of colonic tissues were performed. Results: Re combinant human G-CSF significantly inhibited LPS-induced TNF-${\alpha}$ mRNA expression in THP-1 cells. As for in vivo relevance, G-CSF dramatically reduced the weight loss of mice, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, G-CSF suppressed the expression of tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and intercellular adhesion molecule-1 in TNBS colitis. Conclusion: Current results demonstrate that G-CSF may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

• Clinical and Experimental Reproductive Medicine
• /
• v.28 no.2
• /
• pp.161-167
• /
• 2001

Objective: Granulocyte-macrophage colony stimulating factors known to be secreted in murine and human reproductive tract. The development of human, bovine and murine embryos could be promoted by addition of GM-CSF in culture medium. However, the pregnancy and implantation rate of embryos cultured in GM-CSF have not been evaluated. The aim of this study was to assess the effect of GM-CSF in embryo development, pregnancy and implantation rate. Methods: A total of 191 IVF cycles were divided into control and GM-CSF supplement group (control=96, GM-CSF=95). The embryos were cultured for three day with or without 2 ng/ml of recombinant human GM-CSF. The quality of embryo, developmental velocity, pregnancy and implantation rates were compared. Results: There was no difference in age, number of gonadotropin ampules used, number of oocytes and fertilization. The number of ICSI cycle was higher in GM-CSF group. In GM-CSF group, G-1 grade embryos were the highest in proportion (56.4%), while G-2 grade embryos were highest (44.3%) in control group. The developmental velocity of embryos were not different between GM-CSF and control group. The pregnancy and implantation rates were significantly higher in GM-CSF group than control (47.4% vs. 33.3%, 17.0% vs. 11.1% respectively). Conclusion: By adding GM-CSF in culture medium, the quality of embryo, pregnancy and implantation rate could be improved.

• Clinical and Experimental Reproductive Medicine
• /
• v.29 no.2
• /
• pp.83-90
• /
• 2002

Objective : The purpose of the current series of experiments were to assess the effect of GM-CSF, as a medium supplement, on the development of mouse embryos and the expression of LIF and IL-1? mRNA. Materials and Methods: Mouse 2-cell embryos were collected from the oviducts of 6 weeks old ICR mice at 48 hours after hCG injection. Embryos were cultured in P-1 medium supplemented with mouse GM-CSF (0, 1, 5, 10 ng/ml). The embryo development to blastocysts and hatching blastocysts was assessed and the cell number in blastocyst was also examined. Using RT-PCR, the expressions of LIF and IL-1? mRNA in blastocyst were evaluated in the GM-CSF supplemented group and control group. Results: In mouse, the addition of GM-CSF increased the percentage of blastocysts (65.5%, 68.6%, 73.0% and 76.1% for control and 1, 5 and 10 ng/ml, respectively), and increased the proportion of hatching blastocysts (35.2%, 36.4%, 43.2% and 53.0% for control and 1, 5 and 10 ng/ml, respectively). The mean cell numbers in blastocyst were significantly increased in GM-CSF supplemented groups compared to control group. LIF and IL-1? expression in blastocyst were significantly higher in GM-CSF supplemented group than in control group. Conclusion: The results of experiment by mouse embryos showed beneficial effects of GM-CSF as a medium supplement. Furthermore, the addition of GM-CSF significantly increased the expression of LIF and IL-1? in mouse embryos. These results suggest that GM-CSF might be a important molecule in embryo implantation.

• Biotechnology and Bioprocess Engineering:BBE
• /
• v.9 no.1
• /
• pp.12-16
• /
• 2004

Partitioning of human granulocyte-macrophage colony stimulating factor (hGM-CSF) was achieved in the aqueous two-phase systems (ATPSs) using a crude extract of transgenic tobacco cell suspension culture. This study examined the effects of polyethylene glycol (PEG) molecular weight and concentration and the effects of sodium phosphate concentration in different PEG/sodium phosphate systems on the partition coefficient, K. The best ATPS system was 5% PEG 8,000/1.6 M sodium phosphate after 2 h of incubation at room temperature. In this system, hGM-CSF was partitioned in the PEG-rich phase with a yield of 57.99% and K$\_$hGM-CSF/ of 8.12. In another system, 3% PEG 10,000/1.6 M sodium phosphate, hGM-CSF was also partitioned primarily in the top phase with a yield of 45.66% and K$\_$hGM-CSF/ of 7.64 after 2 h of incubation at room temperature.