• 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.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.17 no.10
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• pp.2395-2402
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• 2013

An active-RC channel selection filter (CSF) with the bandwidth of 40MHz and the improved linearity is proposed in this paper. The proposed CSF is the fifth butterworth filter which consists of a first order low pass filter, two second order low pass filters of a biquad architecture, and DC feedback circuit for cancellation of DC offset. To improve the linearity of the CSF, a body node of a MOSFET for a switch is connected to its source node. The bandwidth of the designed CSF is selected to be 10MHz, 20MHz and 40MHz and its voltage gain is controlled by 6 dB from 0 dB to 24 dB. The proposed CSF is designed by using 40nm 1-poly 8-metal CMOS process with a 1.2V. When the designed CSF operates at the bandwidth of 40 MHz and voltage gain of 0 dB, the simulation results of OIP3, in-band ripple, and IRN are 31.33dBm, 1.046dB, and 39.81nV/sqrt(Hz), respectively. The power consumption and layout area are $450{\times}210{\mu}m^2$ and 6.71mW.

• Proceedings of the Botanical Society of Korea Conference
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• 1999.07a
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• pp.45-49
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• 1999

Plant cell culture is emerging to express bioactive foreign proteins because it has several advantages in that it is safe, economical, genetically stable and eukaryotic expression system comparing with other expression systems. However several limitations such as slow growth rate, low expression level and lack of well established down stream process need to be answered. As a preliminary approach to produce the immunologically interested molecules through the plant cell culture, we tested if granulocyte-macrophage colony stimulating factors (GM-CSFs) from both murine (mGM-CSF) and human (hGM-CSF) are produced as a biologically active form through plant cell culture. The murine and human GM-CSF genes were cloned into the plant expression vector, pBI121, and Ti-plasmid mediated transformation of tobacco leaves was conducted using Agrobacterium tumefaciens harboring both recombinant GM-CSF (rGM-CSF) genes. Cell suspension culture was established from the leaf-derived calli of transgenic tobacco plant. Northern blot analysis indicated the expression of the introduced mGM-CSF gene in both transgenic plant and cell suspension cultures. In addition, the biological activities of both murine and human GM-CSF from plant cell culture were confirmed by measuring the proliferation of the GM-CSF dependent FDC-PI and TF-1 cells, respectively.

• 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.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.7-20
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• 1995

Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$ $Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.

• The Journal of Korean Medicine
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• v.23 no.1
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• pp.11-23
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• 2002

Objectives: We aimed to identify the dose-dependent inhibitory effects of Maekmundongcheongpye-eum and Liriopis Tuber on the mRNA expression of IL-6, IL-16, GM-CSF involved in the asthma model. Methods: In the study BEAS-2B cell lines, human epithelial cells were used. These cells were stimulated with tumor necrosis factor $(TNF)-{\alpha}$ for artificial inflammatory expression. ${\beta}-actin$ messenger RNA (mRNA) was used by internal standard. After 24 hours of Maekmundongcheongpye-eum, Liriopis Tuber-treatment, total cellular RNAs were collected, treating RNAzol directly on the alive cells. Then the transcriptional activities of IL-6, 16, GM-CSF were measured by RT-PCR with electrophoresis. Results: In the Maekmundongcheongpye-eum study, the mRNA expression of IL-6 showed 48% transcriptional inhibitory effect compared to the control group in the $100{\;}{\mu}l/ml$ category (P<0.001). In the IL-16, there was 53% and 57% transcriptional inhibitory effect compared to the control group in the $20{\;}{\mu}l/ml$ and $100{\;}{\mu}l/ml$ categories (P<0.001). In the GM-CSF, there was no inhibitory effect. In the Liriopis Tuber study, the mRNA expression of IL-6 showed 43% transcriptional inhibitory effect compared to the control group in the $100{\;}{\mu}l/ml$ category (p<0.005). In the IL-16, 34% and 26% of transcriptional inhibitory effect was shown compared to the control group in the $20{\;}{\mu}l/ml$ and $100{\;}{\mu}l/ml$ categories, respectively (P<0.05). In the GM-CSF, there was no inhibitory effect. Conclusions: This study shows that Maekmundongcheongpye-eum and Liriopis Tuber have dose-dependent inhibitory effects on the mRNA expression of IL-6 and IL-16 in BEAS-2B cell lines, human epithelial cells. Advanced studies are required to investigate the mechanisms of inhibition by herbal medicine in the asthma model.

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

• 한국생물공학회:학술대회논문집
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• 2002.04a
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• pp.321-324
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• 2002

In situ recovery of recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) was performed in transgenic Nicotiana tabacum cell suspension cultures. Aqueous two-phase systems (ATPS) were used to utilize its biocompatibility. Transgenic plant cells could be grown up to 15.7 g/L in normal medium and 18.6 g/L in ATPS composed of 6% (w/w) polyethylene glycol (PEG) 20,000 and 10% (w/w) dextran 2,000,000. It was proved that the A TPS was not harmful to cell growth. In addition, It is expected to recover hGM-CSF simultaneously with cell growth. Using this method, maximum hGM-CSF concentration at 1.64 ng/mL was obtained on day 3.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.330-330
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• 1994

항암화학요법후 가장 심각한 부작용의 하나는 중성구 감소에 의한 감염이다. 본원에서는 rhGM-CSF을 이용한 제 I상 임상연구에서 150-500$\mu$g/M$^2$/day가 biologically active dose임을 보고한 바 있다. 연자들은 연세암센터에 내원하여 진행성 악성종양으로 병리조직학적 진단을 받고 항암화학요법 시행후 골수억제가 예상되는 환자를 대상으로 GM-CSF 용량에 따른 안전성 및 독성을 검토하고 백혈구 감소증 및 감염의 예방, 치료효과를 분석하여 임상사용권장량을 결정하기위한 2상 연구덜 대상환자의 동의를 얻은후 시행하였다. 대상환자는 37명 (여 26, 남 11)이었고, 항암제는 Adriamycin, Cisplatin, VP-l6 이 주로 사용되었다. 최적임상사용권장량을 결정하기 위하여 1500$\mu\textrm{g}$/M$^2$/day을 12명, 250$\mu\textrm{g}$/M$^2$/day을 12명, 350$\mu\textrm{g}$/M$^2$/day을 13명의 환자에게 투여하였다. 첫번째 항암요법에는 rhGM-CSF을 투여하지않고 (비투여기) 두번째 항암요법에서는 항암요법후 익일부터 10일간 연속, 매일 1회 피하주사하여 (투여기), rhGM-CSF 투여기와 비투여기의 백혈구 감소중 정도의 차이를 비교하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.306-306
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• 1994

항암화학요법후 가장 심각한 부작용의 하나는 중성구 감소에 의한 감염이다. 본원에서는 rhGM-CSF을 이용한 제 I상 임상연구에서 150-500$\mu$g/M$^2$/day가 biologically active dose임을 보고한 바 있다. 연자들은 연세암센터에 내원하여 진행성 악성종양으로 병리조직학적 진단을 받고 항암화학요법시행후 골수억제가 예상되는 환자를 대상으로 GM-CSF 용량에 따른 안전성 및 독성을 검토하고 백혈구 감소증 및 감염의 예방, 치료효과를 분석하여 임상사용권장량을 결정하기위한 2상 연구를 대상환자의 동의를 얻은후 시행하였다. 대상환자는 37명 (여 26, 남 11)이었고, 항암제는 Adriamycin, Cisplatin, VP-16이 주로 사용되었다. 최적임상사용권장량을 결정하기 위하여 1500$\mu\textrm{g}$/M$^2$/day을 12명, 250$\mu\textrm{g}$/M$^2$/day을 12명, 350$\mu\textrm{g}$/M$^2$/day을 13명의 환자에게 투여하였다. 첫번째 항암 요법에는 rhGM-CSF을 투여하지않고 (비투여기) 두 번째 항암요법에서는 항암요법후 익일부터 10일간 연속, 매일 1회 피하주사하여 (투여기), rhGM-CSF 투여기와 비투여기의 백혈구 감소증 정도의 차이를 비교하였다.