Biochemical Properties of a Novel Cysteine Protease of <i>Plasmodium vivax</i> , Vivapain-4

Na, Byoung-Kuk,Bae, Young-An,Zo, Young-Gun,Choe, Youngchool,Kim, Seon-Hee,Desai, Prashant V.,Avery, Mitchell A.,Craik, Charles S.,Kim, Tong-Soo,Rosenthal, Philip J.,Kong, Yoon Public Library of Science 2010 PLoS neglected tropical diseases Vol.4 No.10

<▼1><P><B>Background</B></P><P>Multiple cysteine proteases of malaria parasites are required for maintenance of parasite metabolic homeostasis and egress from the host erythrocyte. In <I>Plasmodium falciparum</I> these proteases appear to mediate the processing of hemoglobin and aspartic proteases (plasmepsins) in the acidic food vacuole and the hydrolysis of erythrocyte structural proteins at neutral pH. Two cysteine proteases, vivapain (VX)-2 and VX-3 have been characterized in <I>P. vivax</I>, but comprehensive studies of <I>P. vivax</I> cysteine proteases remain elusive.</P><P><B>Findings</B></P><P>We characterized a novel cysteine protease of <I>P. vivax</I>, VX-4, of which orthologs appears to have evolved differentially in primate plasmodia with strong cladistic affinity toward those of rodent <I>Plasmodium</I>. Recombinant VX-4 demonstrated dual substrate specificity depending on the surrounding micro-environmental pH. Its hydrolyzing activity against benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA) and Z-Phe-Arg-MCA was highest at acidic pH (5.5), whereas that against Z-Arg-Arg-MCA was maximal at neutral pH (6.5–7.5). VX-4 preferred positively charged amino acids and Gln at the P1 position, with less strict specificity at P3 and P4. P2 preferences depended on pH (Leu at pH 5.5 and Arg at pH 7.5). Three amino acids that delineate the S2 pocket were substituted in VX-4 compared to VX-2 and VX-3 (Ala90, Gly157 and Glu180). Replacement of Glu180 abolished activity against Z-Arg-Arg-MCA at neutral pH, indicating the importance of this amino acid in the pH-dependent substrate preference. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of <I>P. vivax</I>. VX-4 showed maximal activity against actin at neutral pH, and that against <I>P. vivax</I> plasmepsin 4 and hemoglobin was detected at neutral/acidic and acidic pH, respectively.</P><P><B>Conclusion</B></P><P>VX-4 demonstrates pH-dependent substrate switching, which might offer an efficient mechanism for the specific cleavage of different substrates in different intracellular environments. VX-4 might function as a hemoglobinase in the acidic parasite food vacuole, a maturase of <I>P. vivax</I> plasmepsin 4 at neutral or acidic pH, and a cytoskeleton-degrading protease in the neutral erythrocyte cytosol.</P></▼1><▼2><P><B>Author Summary</B></P><P><I>Plasmodium vivax</I> affects hundreds of millions each year and results in severe morbidity and mortality. Plasmodial cysteine proteases (CPs) play crucial roles during the progression of malaria since inhibition of these molecules impairs parasite growth. These CPs might be targeted for new antimalarial drugs. We characterized a novel <I>P. vivax</I> CP, vivapain-4 (VX-4), which appeared to evolve differentially among primate <I>Plasmodium</I> species. VX-4 showed highly unique substrate preference depending on surrounding micro-environmental pH. It effectively hydrolyzed benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA) and Z-Phe-Arg-MCA at acidic pH and Z-Arg-Arg-MCA at neutral pH. Three amino acids (Ala90, Gly157 and Glu180) that delineate the S2 pocket were found to be substituted in VX-4. Alteration of Glu180 abolished hydrolytic activity against Z-Arg-Arg-MCA at neutral pH, indicating Glu180 is intimately involved in the pH-dependent substrate preference. VX-4 hydrolyzed actin at neutral pH and hemoglobin at acidic pH, and participated in plasmepsin 4 activation at neutral/acidic pH. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of <I>P. vivax</I>. The differential substrate preferences depending on pH suggested a highly efficient mechanism to enlarge biological implications of VX-4, including hemoglobin degradation, maturation of plasmepsin, and remodeling of the parasite architecture during growth and development of <I>P. vivax</I>.</P></▼2>

Genetic Transformation of Potato using Ascorbate Peroxidase gene

Na Jong-Kuk(라종국),Allen Randy D.,You Young-Sook(유영숙),Song Ye-Sua(송예수),Song Young-Narm(송융남),Lim Hak-Tae(임학태) 한국원예학회 1998 원예과학기술지 Vol.16 No.2

A Study on the Shape of Iron-Core for a Hybrid Electro-Magnetic Suspension System

Young Jin Hwang,Jae Young Jang,Sukjin Choi,Jin Bae Na,Hyun Chul Jo,Chang Young Lee,Tae Kuk Ko Institute of Electrical and Electronics Engineers 2012 IEEE transactions on applied superconductivity Vol.22 No.3

<P>This paper deals with the shape design of the iron-core of a hybrid EMS (electro-magnetic suspension) system. A proto-type hybrid EMS system was developed by Yonsei University in 2010 [1], [2]. It is the first step of study on fundamental technology for advanced railroad systems development. The hybrid EMS system requires cooling systems because it uses superconducting magnets [3], [4]. These cooling systems can influence costs to making and operating the hybrid EMS system. Therefore, a study to reduce the number of cooling systems needs to be carried out in order to economically commercialize the hybrid EMS system. In this paper, a method that reduces the number of cooling systems of the hybrid EMS system was proposed. To achieve this, a small-scale iron-core and coils assembly was fabricated. Using this system, characteristics of levitation force according to the structure of the iron-core was evaluated. Also, numerical analysis using the FEM tool in order to evaluate the levitation force and net force of a full-scale model was performed. This paper can be expected to suggest useful data for the design of a hybrid EMS system.</P>

The 70-Gene Prognostic Signature for Korean Breast Cancer Patients

Kuk Young Na,김구상,Jeong Eon Lee,김희정,Jung-Hyun Yang,안세현,문병인,Ra Mi Kim,Si Mon Ko,Yong Sik Jung,남석진 한국유방암학회 2011 Journal of breast cancer Vol.14 No.1

Purpose: A 70-gene prognostic signature has prognostic value in patients with node-negative breast cancer in Europe. This diagnostic test known as “MammaPrint^(TM) (70-gene prognostic signature)” was recently validated and implementation was feasible. Therefore, we assessed the 70-gene prognostic signature in Korean patients with breast cancer. We compared the risk predicted by the 70-gene prognostic signature with commonly used clinicopathological guidelines among Korean patients with breast cancer. We also analyzed the 70-gene prognostic signature and clinicopathological feature of the patients in comparison with a previous validation study. Methods: Forty-eight eligible patients with breast cancer (clinical T1-2N0M0) were selected from four hospitals in Korea. Fresh tumor samples were analyzed with a customized microarray for the 70-gene prognostic signature. Concordance between the risk predicted by the 70-gene prognostic signature and risk predicted by commonly used clinicopathological guidelines (St. Gallen guidelines, National Institutes of Health [NIH] guideline, and Adjuvant! Online) was evaluated. Results: Prognosis signatures were assessed in 36 patients. No significant differences were observed in the clinicopathological features of patients compared with previous studies. The 70-gene prognosis signature identified five (13.9%) patients with a low-risk prognosis signature and 31 (86.1%) patients with a high-risk prognosis signature. Clinical risk was concordant with the prognosis signature for 29 patients (80.6%) according to the St. Gallen guidelines; 30 patients (83.4%) according to the NIH guidelines; and 23 patients (63.8%) according to the Adjuvant! Online. Our results were different from previous validation studies in Europe with about a 40% low-risk prognosis and about a 60% high-risk prognosis. The high incidence in the high-risk group was consistent with data in Japan. Conclusion: The results of 70-gene prognostic signature of Korean patients with breast cancer were somewhat different from those identified in Europe. This difference should be studied as whether there is a gene disparity between Asians and Europeans. Further large-scale studies with a follow-up evaluation are required to assess whether the use of the 70-gene prognostic signature can predict the prognosis of Korean patients with breast cancer.

만성 질환과 동반된 치핵의 수술적 치료

나국영 ( Kuk Young Na ),장연수 ( Yeon Soo Chang ),이길연 ( Ku Yeon Lee ),이석환 ( Suk Hwan Lee ),윤충 ( Choong Yoon ) 경희대학교 경희의료원 2005 慶熙醫學 Vol.21 No.2

담낭암에서 Fascin 발현에 대한 연구

나국영(Kuk Young Na),김용호(Yong Ho Kim),김윤화(Youn Wha Kim),홍성화(Sung Wha Hong) 대한외과학회 2008 Annals of Surgical Treatment and Research(ASRT) Vol.75 No.2

Purpose: Gallbladder carcinoma is the most common malignancy of the biliary tract in Koreans. However the exact histopathological characteristics and its carcinogenesis are not well understood. Fascin is an actin bundling protein, and it induces membrane protrusions and increased cell motility in various transformed cells. The expression of fascin is known to be greatly increased in various human neoplasms, but its expression in gallbladder carcinoma is unknown. Methods: A total 110 cases of gallbladder carcinoma, six cases of carcinoma in situ and 10 cases of chronic cholecystitis were immunohistochemically studied to evaluate the expression of fascin in the light of its relationship with various prognostic factors. Results: Seventy eight gallbladder carcinomas (70.9%) showed positive staining for fascin, but none of the chronic cholecystitis and carcinoma in situ was positive. Fascin was strongly stained in the cytoplasm of the cancer cells. The adjacent normal mucosa was negative for fascin staining. There was a significant correlation between lymph node metastasis (P=0.039) and the presence of residual tumor (P=0.016) but there was no significant correlation between age, gender, tumor invasion, histologic difference, neural invasion, lymphatic invasion, stage and recurrence. The 5-year overall survival rate of the fascin positive and negative groups were 48.5% and 53.8%, respectively (P=0.236). On the multivariate analysis, a fascin expression was not significant. Conclusion: Our results suggest that a fascin expression is strongly associated with neoplastic progression in gallbladder carcinomas and fascin positive gallbladder carcinomas show more aggressive behavior.

Diphenylcyclopropenone 감작에 관한 연구

이국형(Kuk Hyeong Lee),김도원(Do Won Kim),나건연(Gun Yoen Na),김점용(Jum Young Kim),서기석(Ki Suk Suh) 대한피부과학회 1991 대한피부과학회지 Vol.29 No.3

N/A A Study of Diphenylcyclopropenone Contact Senaitization Kuk Hyeong Lee, M.D., Do Won Kim, M.D., Gun Yoen Na, M.D.*, Jum Young Kim, M.D.,*, Ki Suk Suh, M.D.** Depertment of Dermatology, Kyungpook National University School of Medicine, Taegu, Korea Department of Dermatology, Pusan Armed Forces General Hospital, Pusan, Korea* Department of Dermatology, Kosin Medical College & Kosin Medical Center, Pusan, Korea** To facilitate measurement of cell mediated immune responses in the healthy adult, a method for quantitative clinical evaluation of contact sensitization to dipheny-lcyclopropenone(DPCP) was devised. Subjects consisted of 77 healthy men(21-24 years old) who were divided into four groups based on concentrations used in sensitization:4%(16 subjects), 2%(21 subject), 1%(20 subjects), and 0,5%(20 subject) DPCP. Each subject received a single 2cm topical application of 0.1ml of DPCP solution in acetone on the shoulder, which was washed it 48 hours later. Sensitization was expressed by the occurence of a sopntaneous flare-us(SFU) after eight to 16 days or a positive reponse on low concentration challenge on day 7, 14 and 21. The over-all rate of sensitization was 88.3%. Sensitization rate did not vary with concentration of DPCP(p>0.005). The average time for SFU occured was 9.9-12.2 days ; a positive response after low concentration challenge test occured on day 14. These results suggests that sensitization of DPCP can be achieved within 2 weeks by a single topical application of 0.1ml of 0.5% DPCP (Kor J Dermatol 29(3) : 292-297, 1991)

예방접종 홍보광고 전략개발 조사연구

오국환(Kuk Hwan Oh),이무식(Moo-Sik Lee),김병희(Byung-Hee Kim),나백주(Ju-Baeg Na),김건엽(Keon-Yup Kim),홍지영(Jee-Young Hong),김영택(Young-Taek Kim),고재영(Jae-Young Go),김영숙(Young-Suk Kim),이석구(Seok-Gu Lee),조형원(Hyung Won Cho) 한국농촌의학 지역보건학회 2005 농촌의학·지역보건 Vol.30 No.2

위암 환자에서 수술 전 혈청 CEA, CA19-9, AFP의 예후 인자로서의 의의

나국영(Kuk-Young Na),장연수(Yeon Soo Chang),김용호(Yong Ho Kim),주선형(Sun Hyung Joo),이석환(Suk-Hwan Lee) 대한외과학회 2008 Annals of Surgical Treatment and Research(ASRT) Vol.75 No.5

Purpose: No tumor-specific markers for gastric cancer are currently known, although various tumor markers have been utilized. CEA, CA19-9 and AFP are the most commonly used tumor markers for gastric cancer. The aim of this study is to evaluate the prognostic significance of the preoperative CEA, CA19-9 and AFP levels in patients with gastric cancer. Methods: A total of 366 patients who underwent curative surgery for gastric cancer were analyzed. The clinicopathologic characteristics and disease-free survival rate of the patients were compared between the positive and negative CEA, CA19-9 and AFP groups of patients, respectively. Also, the prognostic significance of each tumor marker was assessed by multivariate analysis. Results: The CEA, CA19-9 and AFP levels were elevated in 14.2%, 7.9% and 19.1% of the patients, respectively. Serosal invasion and advanced cancer were more frequently found in the groups of patients who were positive for CEA and CA19-9 (P<0.05). More lymph node metastasis and an advanced tumor stage were found in the group of patients who were positive for CA19-9 (P<0.05). On univariate analysis, the disease-free survival rate was significantly lower in the CA19-9 positive group (P<0.05). Serosal invasion and lymph node metastasis were the only significant prognostic factors on multivariate analysis. Conclusion: CEA, CA19-9 and AFP have proved unhelpful for the early detection of gastric cancer due to the low positive rate. CEA and AFP have no prognostic significance and only CA19-9 can be useful for estimating the severity of gastric cancer and as a limited prognostic factor for gastric cancer patients.

Typha orientalis inhibits inflammatory cytokine expression through suppression of ERK phosphorylation in HMC-1 cells

Choi, In-Young,Na, Ho-Jeong,Um, Jae-Young,Kim, Hyung-Min,Hong, Seung-Heon,Sim, Kuk-Jin,Song, Bong-Keun,Nam, Gi-Hye,Choung, Se-Young,Jeong, Hyun-Ja Kyung Hee Oriental Medicine Research Center 2010 Oriental pharmacy and experimental medicine Vol.10 No.1

Typha orientalis' stem (TOS) is traditionally used as an herbal medicine for difficulty in urination, galactophoritis purulenta, whooping cough, and allergic dermatitis. However, its effect in experimental models remains unknown. Here, we report the effect of TOS on the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced inflammatory cytokine production and extracellular signal-regulated kinase (ERK) activation in the human mast cell line, HMC-1. TOS inhibited PMA plus A23187-induced cytokines such as tumor necrosis factor-alpha (TNF-$\alpha$) and interleukin (IL)-6. Maximal inhibition rate of TNF-$\alpha$ and IL-6 production by TOS (1 mg/ml) was about 44.02%, and 45.20%, respectively (P < 0.05). In addition, TOS inhibited the expression of TNF-$\alpha$ and IL-6 mRNA under the same condition. Moreover, TOS partially blocked PMA plus A23187-induced ERK phosphorylation. These results suggested TOS could inhibit the cytokine production through blocking of ERK activity.