Stress-induced Neuroimmuno Alterations in the Rat

Hyun-ju Lee,Kyung Soo Kim,Insop Shim 대한스트레스학회 2010 스트레스硏究 Vol.18 No.2

스트레스는 서로 상호작용을 하는 중추신경계, 내분비계 그리고 면역계에 영향을 준다. 구금스트레스는 시상하부-뇌하수체-부신피질로 이어지는 축(Hypothalamic-pituitary-adrenal axis, HPA-axis)을 활성화시키고 전 염증성, 항 염증성 사이토카인 발현에도 변화를 초래한다. 청반(locus coeruleus)은 스트레스에 반응하는 뇌간의 부분으로 시상하부의 뇌실곁핵에 투사하므로 HPA-축의 활성화에 영향을 끼친다. 본 논문에서는 구금스트레스로 인한 HPA-축 호르몬과 항염증성 사이토카인인 인터루킨-4의 발현 변화를 관찰하고 HPA-축의 최종 호르몬인 코르티코스테론을 주입하였을 때 인터루킨-4의변화를 관찰함으로써, 스트레스 하에서 HPA-축과 인터루킨-4의 상호작용에 대해 밝히고자 하였다. 또한, 면역조직화학법을 통해 청반에서 인터루킨-4를 발현하는 신경세포를 동정하고자 하였다. 실험결과 급성 구속 스트레스에 의해 증가되었던 HPA-축 호르몬들은 반복 구속스트레스를 받았을 때 유의하게 감소하여 지속적인 스트레스에 대한 적응 양상을 나타내었다. 또한, 급성 또는 반복 스트레스를 받았을 때와 코르티코스테론을 반복적으로 주입하였을 때 청반에서의 인터루킨-4 발현이 감소함을 보였다. 이러한 결과는 스트레스 상황에서 활성화 된 HPA-axis가 청반과 상호작용을 하여 인터루킨-4 발현을 감소시킴을 시사한다. Severe stress such as immobilization (IMO) affects the central nervous system, the endocrine system and the immune system that interact each other. IMO-induced responses are activation of hypothalamic-pituitary-adrenal (HPA) axis and production of inflammatory cytokine. The locus coeruleus (LC), which is known to play a role in modulating stress response, innervates the paraventricular neucleus (PVN) of the hypothalamus thereby activating HPA-axis. In this study, IMO-induced alterations of HPA-axis hormones and interleukin-4 (IL-4) were investigated. The final hormone of HPA-axis, corticosterone (CORT) was injected to clarify the interaction of the HPA-axis and IL-4 in the stress response. Single exposure of stress resulted in an increase of corticotrophin-releasing factor expression in the PVN, adrenocorticotropin hormone and CORT levels in the serum. Increased expressions of HPA-axis hormones in the acute stressed group were decreased in repeated stressed group. IL-4 level in the LC of the brain was decreased in both stressed group and repeated CORT injected group. These results suggest the possibility of stress-induced interplay of HPA-axis and IL-4 in the LC.

다중단일염기시발체확장반응을 이용한 한국인에서의 혈소판항원검사

홍윤지,박경운,장호은,정유선,이화진,현정원,황상미,김택수,송정한,한규섭 대한수혈학회 2013 大韓輸血學會誌 Vol.24 No.2

Background:Alloimmunization of human platelet antigens (HPA) is associated with clinically significant disease, such as platelet refractoriness, neonatal alloimmune thrombocytopenia, or posttransfusion purpura. It is determined by single nucleotide polymorphism of genes for platelet membrane glycoprotein. To date, approximately 27 HPAs have been discovered, and their frequencies differ depending on ethnicity and country. Methods:We conducted an investigation of prevalence of HPA in the Korean population using a multiplex single-base primer extension reaction (SNaPshot). With 84 specimens from healthy donors, HPA genotyping was performed on 11 different HPAs, including HPA-1, -2, -3, -4, -5, -6, -7, -8, -9, -13, and -15. Results:A total of 90 blood samples were genotyped. The genotype frequencies of HPA were as follows: HPA-1a/1a: 100.0%, -2a/2a: 83.3%, -2a/2b: 14.3%, -2b/2b: 2.4%, -3a/3a: 39.3%, -3a/3b: 52.4%, -3b/3b: 8.3%, -4a/4a: 100.0%, -5a/5a: 95.2%, -5a/5b: 4.8%, -6a/6a: 94.0%, -6a/6b: 6.0%, -7a/7a: 100.0%, -8a/8a: 100.0%, -9a/9a: 97.6%, -9a/9b: 2.4%, -13a/13a: 100.0%, -15a/15a: 23.8%, -15a/15b: 51.2%, and -15b/15b: 25.0%. Conclusion:The SNaPshot assay was employed for detection of SNPs in various clinically significant HPA genes. In addition to well-known frequencies of previously reported HPA-1 to -8, this study showed frequencies of HPA-9, -13, and -15 in Koreans for the first time. The SNaPshot technique might be suitable for use in actual clinical testing in patients with platelet alloimmunization. 배경: 사람혈소판항원(human platelet antigen, HPA)과 관련된 동종면역은 혈소판불응증, 신생아동종면역혈소판감소증, 수혈후자반과 같은 다양한 임상질환을 일으킨다. 이는 주로 혈소판막의 당단백 발현에 관여하는 유전자의 단일염기다형성(single nucleotide polymorphism, SNP)에 의해결정된다. 현재까지 약 27개의 사람혈소판항원이알려졌고, 그 빈도는 인종에 따라 다르다. 방법: 다중단일염기시발체확장반응(multiplex single- base primer extension reaction, SNaPshot)에 기반한 혈소판항원의 유전형분석기법을 통해 한국인에서의 사람혈소판항원의 빈도를 알아보았다. 신생아동종면역혈소판감소증 의심환아의 부모와 건강한 헌혈자로부터 얻어진 90 검체에 대해유전형분석을 시행하여 HPA-1, -2, -3, -4, -5, -6, -7, -8, -9, -13, -15를 확인하였다. 결과: 90 검체에 대해 유전형분석이 시행되었다. 혈소판항원의 유전형분석의 결과에 따르면HPA-1a/1a: 100.0%, -2a/2a: 83.3%, -2a/2b: 14.3%, -2b/2b: 2.4%, -3a/3a: 39.3%, -3a/3b: 52.4%, -3b/3b: 8.3%, -4a/4a: 100.0%, -5a/5a: 95.2%, -5a/5b: 4.8%, -6a/6a: 94.0%, -6a/6b: 6.0%, -7a/7a: 100.0%, -8a/8a: 100.0%, -9a/9a: 97.6%, -9a/9b: 2.4%, -13a/13a: 100.0%, -15a/15a: 23.8%, -15a/15b: 51.2%, and -15b/15b: 25.0%이었다. 결론: 임상적 의의가 명확한 대표적인 혈소판항원의 유전형을 신속하고 정확하게 분석하기 위해 분자진단기법인 다중단일염기시발체확장반응을 적용하였다. HPA-1부터 -8의 한국인에서의빈도는 기존에 알려진 빈도와 유사한 결과를 나타내었고, -9, -13, -15의 빈도는 이번 연구를 통해처음으로 확인할 수 있었다. 다중단일염기시발체확장반응을 통한 혈소판항원의 유전형분석기법은 향후 혈소판불응증 및 신생아동종면역혈소판감소증 등의 원인을 규명하기 위한 실질적인 임상검사로 사용될 수 있을 것이다.

16-QAM과 16-DAPSK 시스템에서 HPA의 비선형 왜곡을 보상하기 위한 선형화 기술

장경수(Kyeongsoo Jang),유흥균(Heung-Gyoon Ryu) 대한전자공학회 2017 전자공학회논문지 Vol.54 No.10

The immunomodulatory effect of antimicrobial peptide HPA3P restricts <i>Brucella abortus</i> 544 infection in BALB/c mice

Arayan, Lauren Togonon,Kim, Hyeun Bum,Bernardo Reyes, Alisha Wehdnesday,Xuan Huy, Ngoc Tran,Hong, Il Hwa,Lee, Kangseok,Yeom, Ji-Hyun,Park, Yoonkyung,Kim, Suk Elsevier 2018 Veterinary microbiology Vol.225 No.-

<P><B>Abstract</B></P> <P>The discovery of antimicrobial peptides (AMPs) in recent years has been promising for the treatment of multidrug resistant pathogenic microbes. Brucellosis is still considered one of the most common zoonoses in the world. In this study, we evaluated the effect HPA3P peptide in the bacterial uptake and intracellular growth of <I>Brucella abortus</I> (<I>B. abortus)</I> 544 in murine macrophages RAW 264.7. HPA3P was further utilized in a mouse model for infection and treatment. This peptide did not show cytotoxicity or bactericidal effect to <I>B. abortus</I>. However, it inhibited bacterial internalization at 0, 15 and 30 min incubation at two different doses at 12 and 24 μM as well as reduced intracellular growth after 2, 24 and 48 h incubation. Mice treated with HPA3P demonstrated a significant 1.01-log reduction (<I>P < </I>0.0001) and spleen weight reduction compared to the nanocarrier control (<I>P < </I>0.01). Significant increases in key cytokines Interferon-γ (IFN-γ) and Tumor necrosis factor (TNF) at 3, 7 and 14 days post-infection were observed in HPA3P treated mice similar to the antibiotic control group with both compared to the nanocarrier control. Monocyte chemoattractant protein-1 (MCP-1) was also heightened at 14 days post-infection. Histopathological analysis also suggests reduced bacterial granuloma in the liver and spleens of HPA3P treated group compared with the nanocarrier control group. In this study, the modulation of crucial cytokines IFN-γ and TNF might have led to a considerable reduction in the proliferation of <I>B. abortus</I> in a mouse model of brucellosis. Further investigation might be required to maximize the efficacy of HPA3P treatment in murine brucellosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> HPA3P did not cause any cytotoxicity or bactericidal effect to <I>B. abortus</I>. </LI> <LI> HPA3P inhibited bacterial internalization and reduced intracellular growth within macrophages. </LI> <LI> Mice treated with HPA3P demonstrated a significant log reduction and spleen weight reduction compared to the nanocarrier control. </LI> <LI> Significant increases in key cytokines IFN-γ and TNF were observed in HPA3P treated mice. </LI> <LI> Histopathological analysis suggests reduced bacterial granuloma in the liver and spleens of HPA3P treated group compared to nanocarrier group. </LI> </UL> </P>

간섭채널에서 비선형 위성 통신 시스템의 특성 분석

박주석,유흥균,김기근,이대일,김도선 한국통신학회 2004 韓國通信學會論文誌 Vol.29 No.2A

위성 통신 시스템은 지상국과 위성에서 고출력의 비선형 HPA(high power amplifiers)를 사용하게 된다. 그러므로 HPA의 비선형성이 통신 시스템에 미치는 영향을 고려하는 것이 중요하다. 본 연구는 비선형성 HPA에 의한 전력 스펙트럼 밀도 변화와 IBO(input back-off)에 따라 신호의 왜곡과 하모닉 성분의 크기 변화를 구한다. 그리고 BPSK 위성 통신 시스템에서, HPA에 의한 인접 채널 간섭(ACI : adjacent channel interference) 및 외부 재밍 간섭 등에 의한 동일채널 간섭(CCI : co-channel interference)를 고려하여 성능분석을 한다. 일정한 uplink SNR(signal to noise power ratio), uplink SIR(signal to co-channel interference power ratio), downlink SIR인 상황에서, 인접 채널 간섭의 크기에 따른 BER 성능 변화를 구한다. 위성에만 비선형 HPA가 있을 경우는, 비선형에 의한 인접 채널 간섭의 크기에 따라 성능에 많은 차이가 있음을 확인하였다. 그리고 지상국과 위성에서 모두 비선형 왜곡이 있을 때, CCI와 인접 채널 간섭에 의하여 더욱 성능이 저하된다. Satellite communication system uses a high non-linear HPA(high power amplifiers) in the earth station and satellite transponder. Therefore, it is important to consider the nonlinear effect of HPA on the communication system. In this paper, we find the variation of power spectrum density by nonlinearity HPA and the change of harmonic component according to IBO (input back-off). When the BPSK is used for satellite communication system, we analyze BER performance including the external co-channel interference (CCI) and the adjacent channel interference (ACI) resulting from the HPA nonlinearity. BER degrades as ACI magnitude grows up when the uplink SNR, uplink SIR (signal to co-channel interference power ratio) and downlink SIR are constant at some level. In case there is only non-linear HPA in the satellite, it is shown that BER considerably depends on the ACI magnitude ACI. When there are two non-linear HPAs in the both earth station and satellite, much BER degradation results from the CCI and ACI.

Effect of Leucine and Lysine substitution on the antimicrobial activity and evaluation of the mechanism of the HPA3NT3 analog peptide

Gopal, Ramamourthy,Park, Seong-Cheol,Ha, Kyeoung-Ju,Cho, Seung Joo,Kim, Si Wouk,Song, Peter I.,Nah, Jae-Woon,Park, Yoonkyung,Hahm, Kyung-Soo John Wiley Sons, Ltd. 2009 Journal of Peptide Science Vol.15 No.9

<P>In this study, a HPA3NT3-analog (FKKLKKLFKKILKLK-NH<SUB>2</SUB>) peptide was designed. In this analog, two Trp residues (positions 12, 14) were replaced with Leu, and Arg and Asn (positions 3, 13) were replaced with Lys to investigate the role of amino acid substitution and increased cationicity on antimicrobial and hemolytic activities. In fungal and Gram-negative bacterial cells, HPA3NT3-analog activity was unchanged or slightly enhanced when compared to the HPA3NT3 peptide. In addition, a twofold decrease in activity against Gram-positive bacteria was observed. The HPA3NT3-analog also induced less hemolysis (4.2%) than the HPA3NT3 peptide (71%) at 200 µM. Circular dichroism (CD) spectra revealed that the HPA3NT3-analog peptide had an unordered structure in buffer and egg yolk L-2-phosphatidyl choline (EYPC), but adapted an α-helical conformation in 50% 2,2,2-trifluoroethanol (TFE) and negatively charged egg yolk L-2-phosphatidyl glycerol (EYPG), while the parent peptide showed an ordered structure in the EYPC. Additionally, the HPA3NT3-analog peptide induced the leakage of calcein from egg yolk L-2-phosphatidyl ethanolamine (EYPE)/EYPG (7:3 w/w) large unilamellar vesicles (LUVs); however, the activity was slightly weaker than that of the HPA3NT3 peptide. The molecular dynamics (MD) structures revealed that the amino acid substitutions induced a significant variation in peptide structure. These results suggest that the substitutions of Arg and Asn with Lys and two Trp with Leu resulted in small changes in HPA3NT3-analog activity and significant decreases in hemolytic activity. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.</P>

비선형 HPA 환경을 고려한 4D-8PSK-TCM 시스템의 설계 및 분석

안창영(Changyoung An),유상범(Sang-Burm Ryu),이상규(Sang-Gyu Lee),유흥균(Heung-Gyoon Ryu) 한국전자파학회 2018 한국전자파학회논문지 Vol.29 No.4

본 논문에서는 X밴드 위성통신을 위해 권고되는 4D-8PSK-TCM(Four Dimensional 8-ary Phase Shift Keying Trellis Coded Modulation) 시스템을 비선형 HPA(High Power Amplifier)와 전치왜곡기를 고려하여 설계하고, 스펙트럼, BER(Bit Error Rate) 성능을 평가 및 분석한다. 위성통신에서는 한정적인 전력으로 인해 전력을 가장 많이 소모하는 HPA의 동작점을 결정하는 비선형 특성 분석이 매우 중요하다. 본 논문에서는 2, 2.25 bits/channel-symbol의 효율을 갖는 4D-8PSK-TCM 시스템을 설계하였다. 시뮬레이션 결과로, 낮은 PAPR(Peak to Average Power Ratio) 특성과, 스펙트럼의 점유 대역폭을 기준으로 SRRC(Square Root Raised Cosine) 필터의 Roll-off 값은 0.35가 효율적이며, 전치왜곡기를 사용하지 않을 경우 HPA에서 약 15~20 ㏈의 OBO(Output Back-Off)가 요구되며, 전치왜곡기를 사용할 경우 약 1 ㏈ 내외의 OBO가 요구됨을 확인하였다. Considering a nonlinear high power amplifier(HPA) and a predistorter, we have designed a four-dimensional 8-ary phase shift keying trellis-coded modulation(4D-8PSK-TCM) system, which is recommended for X-band satellite communications. Subsequently, we have evaluated and analyzed the spectrum, constellation characteristics, and BER performance of the system. In satellite communications, owing to the limited power, nonlinear characteristics that determine the operating point of the HPA must be analyzed because the HPA consumes high power. We herein report the design of the 4D-8PSK-TCM system, with efficiencies of 2 and 2.25 bits/channel-symbol. The simulation results confirmed that a 0.35 roll-off value is effective, considering the low peak-to-average power ratio(PAPR) characteristic and the narrow occupation bandwidth of the spectrum. It also confirmed that approximately 15~20 ㏈ of output backoff(OBO) value is required at the HPA when the predistorter is not used, and approximately 1 ㏈ of the OBO value is required when the predistorter is used.

16-QAM 시스템에서 HPA 비선형성을 보상하기 위한 사전왜곡기의 설계 및 성능 평가

장경수,유흥균 한국전자파학회 2017 한국전자파학회논문지 Vol.28 No.12

초고속 통신을 위해 HPA(High Power Amplifier)를 사용할 때, HPA의 비선형 특성은 전력 효율 및 BER(Bit Error Rate) 성능 및 스펙트럼 효율 등을 열화시키는 원인이 된다. 초고속 통신을 위한 충분한 송신 전력을 얻기 위해서는 HPA의 사용이 불가피하므로 사전왜곡기를 사용하여 HPA의 비선형성을 보상시켜줄 필요가 있다. 본 논문에서는 HPA의 비선형성을보상해주기 위한 용도의 사전왜곡기를 HPA의 앞단에 사용하여 비선형 왜곡을 보상하여, 이를 성좌도, 스펙트럼, BER 성능 등으로 비교하여 분석하였다. 시뮬레이션 결과, 사전왜곡기를 사용하여 HPA의 비선형성을 보상해줌으로써 이상적인 선형 증폭기와 비슷한 수준의 BER 성능을 얻을 수 있었으며 스펙트럼 마스크도 충족하는 것을 확인할 수 있었다.

Decolorization Method of Crude Alkaline Protease Preparation Produced from an Alkalophilic Bacillus clausii

Kwang Bon Koo,Han-Seung Joo,최장원 한국생물공학회 2011 Biotechnology and Bioprocess Engineering Vol.16 No.1

Diaion HPA75 decolorized efficiently the crude preparation of novel alkaline protease produced by Bacillus clausii. The optimum concentrations of HPA75 and contact time for efficient decolorization were determined to be approximately 6 ~ 10% (w/v) and 8 h, respectively. Color removal efficiency was improved at alkaline pH, and 21%color intensity was retained with a protease yield of 99.7%at pH 11. By using highly concentrated samples, a pattern of decolorization was achieved that was similar to that produced by unconcentrated enzyme preparations. After treatment with 6% HPA75 for 8 h, the residual color intensity was approximately 20% with a protease yield of nearly 100%. Used HPA75 could be regenerated easily,and the regenerated HPA75 was as effective as the fresh HPA75 for decolorization and protease recovery. The regeneration efficiency of the used Diaion HPA75 was greater than 90% until it was used four times. Considering these results, we suggest Diaion HPA75 is suitable for color removal applications, producing high protease yields from fermented broth.

Stress-induced Neuroimmuno Alterations in the Rat

이현주,김경수,심인섭 대한스트레스학회 2010 스트레스硏究 Vol.18 No.2

Severe stress such as immobilization (IMO) affects the central nervous system, the endocrine system and the immune system that interact each other. IMO-induced responses are activation of hypothalamic-pituitary-adrenal (HPA) axis and production of inflammatory cytokine. The locus coeruleus (LC), which is known to play a role in modulating stress response, innervates the paraventricular neucleus (PVN) of the hypothalamus thereby activating HPA-axis. In this study, IMO-induced alterations of HPA-axis hormones and interleukin-4 (IL-4) were investigated. The final hormone of HPA-axis, corticosterone (CORT) was injected to clarify the interaction of the HPA-axis and IL-4 in the stress response. Single exposure of stress resulted in an increase of corticotrophin-releasing factor expression in the PVN, adrenocorticotropin hormone and CORT levels in the serum. Increased expressions of HPA-axis hormones in the acute stressed group were decreased in repeated stressed group. IL-4 level in the LC of the brain was decreased in both stressed group and repeated CORT injected group. These results suggest the possibility of stress-induced interplay of HPA-axis and IL-4 in the LC. (Korean J Str Res 2010;18:81∼86)