• Title/Summary/Keyword: CSF3

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Selective regulation of osteoclast adhesion and spreading by PLCγ/PKCα-PKCδ/RhoA-Rac1 signaling

  • Kim, Jin-Man;Lee, Kyunghee;Jeong, Daewon
    • BMB Reports
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    • v.51 no.5
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    • pp.230-235
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    • 2018
  • Bone resorption by multinucleated osteoclasts is a multistep process involving adhesion to the bone matrix, migration to resorption sites, and formation of sealing zones and ruffled borders. Macrophage colony-stimulating factor (M-CSF) and osteopontin (OPN) have been shown to be involved in the bone resorption process by respective activation of integrin ${\alpha}v{\beta}3$ via "inside-out" and "outside-in" signaling. In this study, we investigated the link between signal modulators known to M-CSF- and OPN-induced osteoclast adhesion and spreading. M-CSF- and OPN-induced osteoclast adhesion was achieved via activation of stepwise signals, including integrin ${\alpha}v{\beta}3$, $PLC{\gamma}$, $PKC{\delta}$, and Rac1. Osteoclast spreading induced by M-CSF and OPN was shown to be controlled via sequential activation, consistent with the osteoclast adhesion processes. In contrast to osteoclast adhesion, osteoclast spreading induced by M-CSF and OPN was blocked via activation of $PLC{\gamma}/PKC{\alpha}/RhoA$ signaling. The combined results indicate that osteoclast adhesion and spreading are selectively regulated via $PLC{\gamma}/PKC{\alpha}-PKC{\delta}/RhoA-Rac1$ signaling.

Cerebrospinal Fluid Profiles and Their Changes after Intraventricular Chemotherapy as Prognostic or Predictive Markers for Patients with Leptomeningeal Carcinomatosis

  • Kwon, Ji-Woong;Shim, Youngbo;Gwak, Ho-Shin;Park, Eun Young;Joo, Jungnam;Yoo, Heon;Shin, Sang-Hoon
    • Journal of Korean Neurosurgical Society
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    • v.64 no.4
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    • pp.631-643
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    • 2021
  • Objective : Here, we evaluated whether cerebrospinal fluid (CSF) profiles and their changes after intraventricular chemotherapy for leptomeningeal carcinomatosis (LMC) could predict the treatment response or be prognostic for patient overall survival (OS) along with clinical factors. Methods : Paired 1) pretreatment lumbar, 2) pretreatment ventricular, and 3) posttreatment ventricular samples and their CSF profiles were collected retrospectively from 148 LMC patients who received Ommaya reservoir installation and intraventricular chemotherapy. CSF profile changes were assessed by calculating the differences between posttreatment and pretreatment samples from the same ventricular compartment. CSF cell counts were further differentiated into total and other based on clinical laboratory reports. Results : For the treatment response, a decreased CSF 'total' cell count tended to be associated with a 'controlled' increase in intracranial pressure (ICP) (p=0.059), but other profile changes were not associated with either the control of increased ICP or the cytology response. Among the pretreatment CSF profiles, lumbar protein level and ventricular cell count were significantly correlated with OS in univariable analysis, but they were not significant in multi-variable analysis. Among CSF profile changes, a decrease in 'other' cell count showed worse OS than 'no change' or increased groups (p=0.001). The cytological response was significant for OS, but the hazard ratio of partial remission was paradoxically higher than that of 'no response'. Conclusion : A decrease in other cell count of CSF after intraventricular chemotherapy was associated with poor OS in LMC patients. We suggest that more specific CSF biomarkers of cancer cell origin are needed.

A study on feature points matching for 3D reconstruction using Column Space Fitting (CSF) (Column Space Fitting (CSF)을 이용한 3차원 복원을 위한 특징점 매칭에 대한 연구)

  • Oh, Jangseok;Hong, Hyunggil;Woo, Seongyong;Song, Suhwan;Seo, Kapho;Kim, Daehee
    • Proceedings of the Korean Society of Computer Information Conference
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    • 2018.07a
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    • pp.389-390
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    • 2018
  • 본 논문에서는 3차원 복원을 위한 특징점 추출 및 매칭에 대한 보다 정확한 방법을 제안한다. 이 방법은 컴퓨터 비전의 기본이 되는 분야로 복원뿐 만 아니라 SLAM과 같은 지도 작성 및 자율 운행에도 필요한 방법이다. 본 연구는 3차원 물체 복원을 위해서 사용하는 방법 중 하나인 Column space fitting(CSF)을 이용하여 turntable-image data에 적용하여 성능을 평가하여 정확성을 검증을 한다. 오늘날 3D scanner를 이용하여 물체를 3차원 모델을 획득하고 3D프린터를 이용하여 다양한 분야에 적용한다. 그러나 고가의 장비이기 때문에 접근성이 떨어진다. 본 연구는 영상들만을 가지고 기하학적 계산을 통해 3차원 모델을 획득한다. 본 연구결과는 기존의 방법인 KLT 알고리즘과 비교하여 RMSE의 값을 약 5배를 줄이는 성능 향상을 보인다.

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A Study of Peripheral Blood and Bone Marrow Responses Depends on the Frequency of rhG-CSF Administration in Dogs (개에서 재조합 과립구 자극 인자 (rh G-CSF)의 투여 간격에 따른 말초혈액과 골수의 반응에 대한 연구)

  • Kim, Ji-Hyun;Jee, Cho-Hee;Won, Jin-Hee;Jung, Hae-Won;Moon, Jong-Hyun;Cho, Kyu-Woan;Kang, Byeong-Teck;Jung, Dong-In
    • Journal of Veterinary Clinics
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    • v.31 no.2
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    • pp.77-84
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    • 2014
  • The present study evaluated that responses of peripheral and bone marrow depends on the frequency of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration in dogs. The rhG-CSF has been revealed that have a beneficial effect for dogs with myelosuppression secondary to chemotherapy or radiation but there were no studies about the frequency of administration in dogs. In this research, rhG-CSF was administrated $5{\mu}g/kg$ subcutaneously for each two-dogs group as follows: (1) every day for trial, (2) every other day for trial, (3) every third day for trial. The peripheral blood analysis including direct microscopic differential counts of one hundred cells was performed every day. Bone marrow aspiration was performed before administration of rh G-CSF, on the day of 0, 3, 9 and when the WBC counts were decreased within the normal range (day 12 or 13). Rh G-CSF was well-tolerated and showed no side effects in all dogs. According to the present study, $5{\mu}g/kg$ administration of rhG-CSF have cell-specific, frequency-related effect on bone marrow and peripheral blood. Furthermore, the effects of rhG-CSF administration on bone marrow sustained during the study and prolonged at least 3 days after discontinuing of rhG-CSF treatment.

항암약물요법후 골수억제가 수반된 진행암환자에서 rhGM-CSF의 제2상 임상연구: rhGM-CSF의 용량에 대한 효과비교

  • 라선영;이경희;정현철;이혜란;유내춘;김주항;노재경;한지숙;김병수
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.313-313
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    • 1994
  • 대상환자는 40예중 37예에서 평가가 가능하였고 남녀비는 11:26. 중앙연령 42세 이었으며 대상질환은 위선암 12에, 유방암 10예. 골옥종 5예등 이었다. rhGM-CSF에 의한 부작용은 150.250 $\mu\textrm{g}$/$m^2$/d 용량군에서는 Grade I-II의 전신쇠약감, 근육통.심계항진등이 관찰되었으나 특별한 조치없이 회복되었다. 350$\mu\textrm{g}$/$m^2$/d 용량군에서는 8예에서 WHO grade II-III의 전신쇠약, 전신열감, 흉부압박감, 호흡곤란 등을 호소하였고 1예에서 투여 1일러 WHO gradeIII의 피부반응이 나타났으며, 이 중 2예에서는 rhGM-CSF를 250 $\mu\textrm{g}$/$m^2$/d로 감량투여후 상시 증상이 소실되었다. rhGM-CSF 투여전의 대조기와 투여기의 혈액학적 소견 비교시. 평균 중성구 최저치는 세 용량군에서 모두 관찰기에 비해 시험기어서 증가하였고. 평균 총 백혈군 최저치는 150.350 $\mu\textrm{g}$/$m^2$/d 용량군은 차이가 있었고 250 $\mu\textrm{g}$/$m^2$/d 용량군은 차이가 있었으나 통계적 유의성은 없었다. 비혈구치가 최저치에서 4.000/㎣ 이상으로 회복되는 평균일수와 호중구치가 최저치에서 2.000/㎣ 이상으로 회복되는 평균일수는 세 용량군 모두에서 관찰기어 비해 시험기에서 증가하였다. 고용량 항암약물요법후 중성구 감소에 의한 발열은 rhGM-CSF 비투여기에서 18예. rhGM-CSF 투여기에서 8예 관찰되었다고 발열기간은 각각 5-7일. 2-3일 이었다. 임상 양상은 세 용량군 간 차이가 없었으나, 시험기에서 발열의 발현율이 낮았으며, 발열일 수와 항생제 사용일 수가 짧았다. 결론: 골수억제 조절 효과는 용량에 따른 혈액소견에 미치는 영향, 부작용, 감염의 빈도, 감염발생에 따른 항생제 사용기간 등을 고려하여 그 임상 유효성 평가시, 제 3상 시험에 사용할 권장량 (recommended dose) 은 250 ug/$m^2$/d $\times$ 10d 으로 관찰되었다.

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In situ Recovery of hGM-CSF in Transgenic Rice Cell Suspension Cultures (형질전환 벼 현탁세포 배양에서 hGM-CSF의 in situ Recovery 연구)

  • Myoung, Hyun-Jong;Choi, Hong-Yeol;Nam, Hyung-Jin;Kim, Dong-Il
    • KSBB Journal
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    • v.30 no.3
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    • pp.103-108
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    • 2015
  • Production of foreign proteins by transgenic plant cell cultures has several advantages such as post-translational modification, low risk of product contamination and low-cost production and purification. However, target proteins are degraded by extracellular proteases existing in the media. A solution to this problem is the use of perfusion culture and ion exchange chromatography for the application of integrated bioprocess using in situ recovery. With this method, production of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) was investigated in this study. First, optimization of cell concentration during the induction phase for the production of hGM-CSF was examined. As cell concentration increased, the level of hGM-CSF was decreased due to the presence of extracellular proteases. Induction using sugarfree media produced 33% more hGM-CSF. The effects of pH on the binding of hGM-CSF to cationic and anionic exchange resins were also investigated. In terms of stability, optimal pH was found to be 5~7. In the case of using buffer exchange when CM-Sepharose was used as a cationic exchange resin, optimal pH for binding was 4.8 and adsorption yield was 77%. When DEAE-Sepharose was used as an anionic exchange resin, it was 5.5 (74%). Without buffer exchange, optimal pH was 4.6 (84%). From these results, an integrated bioprocess using in situ recovery with simultaneous production and separation of foreign protein in transgenic plant cell suspension cultures was found to be feasible.

Detection and Characterization of 45 kDa Platelet Activating Factor Acetylhydrolase in Cerebrospinal Fluid of Children with Meningitis

  • Moon, Tae-Chul;Kim, Mi-Suk;Lee, Su-Jeong;Lee, Tae-Yoon;Kwon, Soon-Hak;Baek, Suk-Hwan;Chang, Hyeun-Wook
    • Archives of Pharmacal Research
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    • v.26 no.7
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    • pp.554-558
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    • 2003
  • Platelet activating factor acetylhydrolase (PAF-AH) activity has been identified in cerebrospinal fluid (CSF) samples taken from children with meningitis. We reported that PAF-AH activity is significantly increased, by about 3 fold, in patients with meningitis compared to control subjects. Because of limited knowledge about this enzyme in CSF, we examined the biochemical properties of CSF PAF-AH. PAF-AH of CSF was calcium independent, showed a broad pH spectrum and was relatively heat stable. In addition, this enzyme activity was strongly inhibited by phenylmethanesulfonyl fluoride (PMSF), partially inhibited by p-bromophenacylbromide (p-BPB), uninhibited by iodoacetamide, and moderately stimulated by dithiothreitol (DTT). PAF-AH of CSF did not degrade phospholipid with a long chain fatty acyl group at sn-2 position. This enzyme hydrolyzed PAF and oxidatively modified phosphatidylcholine. Furthermore, we identified a monomeric polypeptide with a molecular weight of approximately 45 kDa by Western blot using human plasma PAF-AH antibody. These results suggested that plasma type PAF-AH activity exist in CSF taken from children with meningitis.

Four-Week Intravenous Toxicity of DA-3030 (G-CSF) in Beagle Dogs (Beagle dog에서 DA-3030(G-CSF)의 정맥내 4주간 반복투여 독성)

  • 이영순;조재진;남기환;서광원;강성근;박재학;김원배
    • Biomolecules & Therapeutics
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    • v.2 no.3
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    • pp.260-269
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    • 1994
  • This study was performed to determine the toxic effect of DA-3030(granulocyte-colony stimulating factor, G-CSF) in beagle dogs. DA-3030(G-CSF) was injected intravenously at doses of 115 $\mu\textrm{g}$/kg/day, 11.5 $\mu\textrm{g}$/kg/day and 1.15 $\mu\textrm{g}$/kg/day seven days per week for 28 days. After completion of the treatments, the dog were necropsied. The number of dead animal was zero in all groups. No specific clinical sign was found, either. In hematological results, WBC was significantly increased dose-dependently in treated groups. In histopathological findings, megakaryocyte and rubricyte were found in the liver and spleen at the dose of 115 $\mu\textrm{g}$/kg/day. Therefore, we could find the extramedullary hematopoiesis was increased. Megaka yocyte and rubricyte were increased in bone marrow, too. In conclusion, those signs were estimated the pharmacological effect of DA-3030(G-CSF). According to the results, non toxic dose of DA-3030(G-CSF) was higher than 115 $\mu\textrm{g}$/kg/day.

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A method to prevent cerebrospinal fluid leakage: Reinforcing acellular dermal matrix

  • Lee, Hojune;Eom, Ye Seul;Pyon, Jai-Kyong
    • Archives of Craniofacial Surgery
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    • v.21 no.1
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    • pp.45-48
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    • 2020
  • In neurosurgical cases, problems related to wound healing can vary from simple wound dehiscence to multilayer defects. This study demonstrates an effective method to prevent persistent cerebrospinal fluid (CSF) leakage using reinforcing acellular dermal matrix in neurosurgical patients with wound dehiscence. A 52-year-old woman was admitted for management of recurrent glioblastoma. After tumor removal surgery, the patient experienced sustained CSF leakage from the wound despite reparative attempts. The plastic surgery team performed wound repair procedure after remnant tumor removal by the neurosurgery team. Acellular dermal matrix was applied over the mesh plate to prevent CSF leakage and the postoperative status of the patient was evaluated. No sign of CSF leakage was found in the immediate postoperative period. After 3 years, there were no complications including CSF leakage, wound dehiscence, and infection. We hereby propose this method as a feasible therapeutic alternative for preventing CSF leakage in patients experiencing wound problem after neurosurgical procedures.

The healing effect of rhGM-CSF on uninfected wounds (rhGM-CSF(Leucogen)의 비감염성 상처 치유 효과에 관한 연구)

  • Han, Seung Kyu;Kim, Byung Soo;Kim, Aeree;Seo, Jae Hong;Choi, Chul Won;Shin, Sang Won;Kim, Yeul Hong;Kim, Woo Kyung;Kim, Jun Suk
    • IMMUNE NETWORK
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    • v.1 no.1
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    • pp.32-35
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    • 2001
  • Background: rhGM-CSF has been shown to enhance the migration and proliferation of endothelial cells and to promote keratinocyte growth. This study was tried to evaluate the effect of rhGM-CSF dressing on the uninfected wounds. Methods: Thirty Sprague-dawley white mice(250-300g) were selected in this study. The number of wound with the diameter of 5 mm, was 3 in left and 3 in right at the symmetric sites, respectively. The site of rhGM-CSF dressing was decided by a randomization. rhGM-CSF($Leucogen^{(R)}$) was diluted in the distilled water($5{\mu}g/mL$). The experimental wound group was dressed by l mL of distilled water mixed with rhGM-CSF and control wound group was dressed by l mL of distilled water. The dressing was done, every 24 hours. The criteria of comparison were the duration of wound healing duration, histologic findings and the bacterial culture of wound sites. Results: The duration of wound healing was $10.3{\pm}1.7days$ in experimental group and $10.2{\pm}2.8days$ in control group, without significant difference. There was no specific difference of histologic findings between both groups. The pathogen was not found, at all. Conclusion: It seems to be that rhGM-CSF has no prominent effect on the uninfected wound healing in the mice without immune suppression.

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