• Title/Summary/Keyword: PD-1/PD-L1

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Chiral [Iminophosphoranyl]ferrocenes: Synthesis, Coordination Chemistry, and Catalytic Application

  • Co, Thanh Thien;Shim, Sang-Chul;Cho, Chan-Sik;Kim, Dong-Uk;Kim, Tae-Jeong
    • Bulletin of the Korean Chemical Society
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    • v.26 no.9
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    • pp.1359-1365
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    • 2005
  • A series of new chiral [iminophosphoranyl]ferrocenes, {${\eta}^5-C_5H_4-(PPh_2=N-2,6-R_2-C_6H_3)$}Fe{${\eta}^5-C_5H_3-1-PPh^2-2-CH(Me)NMe_2$} (1: R = Me, $^iPr$), {${\eta}^5{-C_5H_4-(PPh_2=N-2,6-R_2}^1-C_6H_3)$}Fe{${\eta}^5-C_5H_3-1-(PPh_2=N-2,6-R_2-C_6H_3)-2-CH(Me)R_2$} (2: $R^1\;=\;Me,\;^iPr;\;R^2\;=\;NMe_2$, OMe), and $({\eta}^5-C_5H_5)Fe${${\eta}^5-C_5H_4-1-PR_2-2-CH(Me)N=PPh_3$} (3:R = Ph, $C_6H_{11}$) have been prepared from the reaction of [1,1'-diphenylphosphino-2-(N,N-dimethylamino) ethyl]ferrocene with arylazides (1 & 2) and the reaction of phosphine dichlorides ($R_3PCl_{2}$) with [1,1'-diphenylphosphino-2-aminoethyl]ferrocene (3), respectively. They form palladium complexes of the type $[Pd(C_3H_5)(L)]BF_4$ (4-6: L = 1-3), where the ligand (L) adopts an ${\eta}^2-N,N\;(2)\;or\;{\eta}^2$-P,N (3) as expected. In the case of 1, a potential terdentate, an ${\eta}^2$-P,N mode is realized with the exclusion of the –=NAr group from the coordination sphere. Complexes 4-6 were employed as catalysts for allylic alkylation of 1,3-diphenylallyl acetate leading to an almost stoichiometric product yield with modest enantiomeric excess (up to 74% ee). Rh(I)-complexes incorporating 1-3 were also prepared in situ for allylic alkylation of cinnamyl acetate as a probe for both regio- and enantioselectivities of the reaction. The reaction exhibited high regiocontrol in favor of a linear achiral isomer regardless of the ligand employed.

Activation of Phospholipase Cγ by Nitric Oxide in Choriocarcinoma Cell Line, BeWo Cells (Choriocarcinoma 세포주 BeWo 세포에서 nitric oxide에 의한 phospholipase Cγ 의 활성)

  • 차문석;곽종영
    • Journal of Life Science
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    • v.13 no.6
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    • pp.849-855
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    • 2003
  • Nitric oxide (NO) plays an important role as a signaling molecule in the proliferation of placenta trophoblasts. In this study, we investigated the effect of NO on the activation of phospholipase C (PLC) in BeWo cells, choriocar-cinoma cell line. Sodium nitroprusside (SNP), an agent to produce NO spontaneously in cells, alone increased $[^3H]$ thymidine incorporation of BeWo cells, indicating NO stimulates proliferation of the cells. NO-induced proliferation of BeWo cells was blocked by U73122, an inhibitor of PLC, suggesting that NO-induced PLC activation is involved in the cell proliferation. NO also stimulated extracellular signal-regulated kinase (ERK) in BeWo cells, indicated by increased phosphorylation of ERK1/2 in Western blotting using anti-phospho-ERK1/2 antibody. NO-induced phos-phorylation of ERK1/2 was not abrogated by U73122. $PLC\gamma_1$l but not$PLC\gamma_2$ was tyrosine phosphorylated by SNP in immunoprecipitation assay using anti-$PLC\gamma_1$/$PLC\gamma_2$ antibodies, and SNP-induced phosphorylation of $PLC\gamma_1$ was abrogated by pre-treatment of cells with genistein and PD98059, indicating that NO induced-phosphorylation of $PLC\gamma_1$ is mediated by ERK. These results suggest that NO stimulates the proliferation of BeWo cells through ERK and $PLC\gamma_1$.

Electrical Properties of Multilayer Chip Varistors in the Response Surface Analysis (반응표면분석법에 의한 적층 칩 바리스터의 전기적 특성)

  • Yoon, Jung-Rag;Jeong, Tae-Seok;Choi, Keun-Mook;Lee, Seok-Weon
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.20 no.6
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    • pp.496-501
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    • 2007
  • In order to enhance sintering characteristics on the $ZnO-Pr_6O_{11}$ based multilayer chip varistors (MLVs), a response surface analysis using central composite design method were carried out. As a result, varistor voltage($V_{1mA}$), nonlinear coefficient ($\alpha$), leakage current ($I_L$) and capacitance (C) were considered to be mainly affected by sintered temperature and holding time. MLVs sintered at $1200^{\circ}C$ and above $1200^{\circ}C$ revealed poor electrical characteristics, possibly due to the reaction between electrode materials(Pd) and $ZnO-Pr_6O_{11}$ based ceramics. On the sintering temperature range $1150{\sim}1175^{\circ}C$, nonlinear coefficient ($\alpha$) and leakage current ($I_L$) were shown to be $60{\sim}69$ and below $0.3{\mu}A$, respectively. In particular, MLVs sintered at $1175^{\circ}C$, 1.5 hr and $2^{\circ}C/hr$ (cooling speed) showed stable ESD(Electrical Static Discharge) characteristics under the condition of 10 times at 8 Kv with deviation varistor voltage, and deviation nonlinear coefficient were 0.3% and 0.33% (at positive), 0.55% (at negative), respectively.

Dosimetry of Brachytherapy Sources: Review of The AAPM TG-43 Formalism

  • Cho, Sang-Hyun
    • Proceedings of the Korean Society of Medical Physics Conference
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    • 2002.09a
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    • pp.141-143
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    • 2002
  • In 1995, the American Association of Physicists in Medicine (AAPM) Task Group 43 published a report dealing with the dosimetry of interstitial brachytherapy sources, generally known as the TG-43 report. Compared to previously adopted formalisms, a formalism proposed in this report provides a more accurate and systematic brachytherapy dose calculation method, especially for Ir-192 and other low energy gamma sources such as 1-125 and Pd-l03. In this lecture, an overview of the TG-43 formalism will be presented, along with the lecturer's experience in determining the TG-43 parameters by the Monte Carlo method and experimental methods such as TLD and radiochromic film.

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Effects of Ginseng Saponins on the Development and Loss of Morphine Tolerance and Dependence

  • Kim, Hack-Seang;Oh, Sei-Kwan;Choi, Kang-Ju;Park, Jung-Sup
    • Korean Journal of Pharmacognosy
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    • v.17 no.2
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    • pp.139-147
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    • 1986
  • Ginseng saponins(GS), protopanaxadiol saponins(PD) and protopanaxatriol saponins (PT) were tested for the inhibition of the development of morphine tolerance and dependence antagonism of morphine analgesia and the loss of morphine tolerance and dependence in mice The results were as follows: 1. Inhibition of the development of morphine tolerance and dependence. 2. Antagonism of morphine analgesia. 3. Increase in the loss of morphine tolerance and dependence. Antagonism of morphine by ginseng saponins and its reversal by L-DOPA and 5-HTP suggest some possibility that catecholamines and serotonin levels might be associated with the results.

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The Inflammation-modulatory Effects of Ginseng Saponin and Polysaccharide on Activated RAW264.7 Cell-line (인삼 사포닌과 다당류 혼합물의 활성화된 RAW264.7 세포주에 대한 염증조절 효과)

  • Lee, Do-Ik
    • YAKHAK HOEJI
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    • v.54 no.2
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    • pp.134-141
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    • 2010
  • It is well known that the numbers and functions of immune-associated cells are increased by saponins and polysaccharides in ginseng. In this study, the mixture of polysaccharide and saponin (MPS) from Panax ginseng is applied to LPS- activated RAW 264.7 cells. The production of NO and the gene expression of IL-6 and TNF-$\alpha$ are decreased in LPSactivated RAW 264.7 cells and the expression of arginase II and PD-1L genes is decreased in LPS-untreated macrophages. Therefore, the mixture of saponin and polysaccharide from Panax ginseng could be used in order to regulate immune responses.

NLRC4 Inflammasome-Mediated Regulation of Eosinophilic Functions

  • Ilgin Akkaya;Ece Oylumlu;Irem Ozel;Goksu Uzel;Lubeyne Durmus;Ceren Ciraci
    • IMMUNE NETWORK
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    • v.21 no.6
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    • pp.42.1-42.20
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    • 2021
  • Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

Effects of Cadmium on Glucose Transport in L6 Myocytes (L6 근육세포에서 포도당 수송능에 미치는 $CdCl_2$의 영향)

  • Kang Donghee;Khil Lee-Yong;park Kwangsik;Lee Byung-Hoon;Moon Chang-Kiu
    • Environmental Analysis Health and Toxicology
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    • v.20 no.1
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    • pp.75-85
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    • 2005
  • This study was aimed to know the effect of cadmium chloride (CdCl₂) on glucose transport in L6 myotube and its action mechanism. CdCl₂ increased the 2-deoxy- (l-3H)-D-glucose (2-DOG) uptake 1.9 and 2.4 fold at 10 and 25 μM respectively. To investigate the stimulating-mechanism of glucose transport induced by CdCl₂, the wortmannin and PD98059 were used as PI3K (phosphatidylinositol 3-kinase) inhibitor and MAPK inhibitor respectively, which did not affect 2-DOG uptake. This fact suggests that CdCl₂ induced 2-DOG uptake may not be concerned to the insulin signalling pathway. Whereas nifedipine, a calcium channel blocker, and trifluoperazine, a calmodulin inhibitor, were found to inhibit the 2-DOG uptake stimulted by CdCl₂. In addition, we also measured the ROS (reactive oxygen species) production and GSH level in L6 myotube to investigate the correlation between the glucose uptake and ROS. CdCl₂(25 μM) increased ROS generation approximately 1.5 fold and changed the cellular GSH level, but GSSG/GSH ratio remained unchanged. CdCl₂ stimulated 2-DOG uptake and ROS generation were inhibited by N-acetylcystein. And BSO pretreatment, a potent inhibitor of γ-GCS, resulted in the dramatic decrease of 2-DOG uptake and also the increase of the sensitivity to cadmium cytotoxicity. The obtained results suggest that CdCl₂-stimulated glucose uptake might be based on the activation of HMP shunt as an antioxidant defense mechanism of the cells.

HPLC Determination and Pharmacokinetics of Endogenous Acetyl-L-Carnitine (ALC) in Human Volunteers Orally Administered a Single Dose of ALC

  • Kwon, Oh-Seung;Chung, Youn-Bok
    • Archives of Pharmacal Research
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    • v.27 no.6
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    • pp.676-681
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    • 2004
  • Acetyl-L-camitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer's type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, valida-tion of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacok-inetics after oral administration of ALC to human volunteers. ALC concentrations in human plasma were corrected by subtracting the concentration of blank plasma from each sample. Precision and accuracy (bias %) for uncorrected ALC concentrations were below 2.6 and 6.5% for intra-days, and 4.0 and 9.4% for inter-days, respectively. Precision and accuracy (bias %)for corrected ALC concentrations were below 10.9 and 6.0% for intra-days, and 10.5 and 16.9% for inter-days, respectively. Quantitation limit was $0.1{\;}\mu\textrm{g}/mL$. After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the principle pharmacokinetic parameters were 4.2 h of the half-life$ (t_{1/2},{\beta})$, the area under the curve $(AUC_{0{\rightarrow}8){\;}of{\;}9.88{\;}\mu\textrm{g}{\cdot}h/mL$, and 3.1 h of the time ($T_{max}$) to reach $C_{max}$. This study first describes the pharmacokinetic study after oral admin-istration of a single dose of ALC in human volunteers.

Field Test of Optical Voltage and Current Meter (광 응용 전류 전압계의 현장실험)

  • Kim, K.C.;Song, J.T.;Song, W.S.;Kim, C.S.;Lee, K.C.;Lee, S.I.
    • Proceedings of the KIEE Conference
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    • 1992.07b
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    • pp.794-798
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    • 1992
  • We present an optical Voltage and current sensor using $BSO(Bi_{12}SiO_{20})$ monocrystal. The voltage and current sensor consist of PBS(Polarizing Beam Splitter), 1/4 wavelength plate, ZnSe, Selfoc lens, LED, and PIN-PD etc. Magnetic core was made using permalloy for applying magnetic field to current sensor effectively. Current was measured from 100 to 1,600 ampere and accuracy was about ${\pm}$5%. The accuracy could be improved to ${\pm}$l% after reducing the nonlinear property of BSO crystal using our own program in PC (IBM286). We noticed that these data were not influenced by 154,000 voltage at all. Applied voltage was reduced to 1/20 using capacitors. And experiment was carried out up to 450V of the reduced voltage. The data fran optical voltage sensor was similar to that from conventional voltage sensor. The accuracy of the data was within about ${\pm}$1%.

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