병원획득 Klebsiella pneumoniae 균혈증 분석을 통해 본 Ciprofloxacin 내성과 Extended-Spectrum β-Lactamase생성 간의 연관성

김미영,추은주,곽이경,송문희,나성수,송태준,김성혜,전재범,최상호,정진용,김남중,김양수,우준희,류지소 대한감염학회 2004 감염과 화학요법 Vol.36 No.5

목적 : K. pneumoniae는 ciprofloxacin내성 증가가 전세계적으로 문제가 되고있는 extended-spectrum beta-lactamase (ESBL)를 생성하는 대표적인 세균으로 최근 외국에서 ciprofloxacin 내성과 ESBL 생성사이에 관련이 있다는 2-3편의 보고들이 있었다. 본 연구에서는 병원획득 K. pneumoniae 패혈증이 있었던 환자들을 대상으로 ciprofloxacin 내성과 관련된 인자를 알아보고자 하였다. 재료 및 방법 : 2001년 1월 부터 2002년 12월 사이에 2200병상의 3차 의료기관인 한 대학병원에서 입원 후 72시간 이후에 나간 혈액배양에서 K. pneumoniae가 배양된 입원환자를 대상으로 의무기록과 전산기록을 분석하여 환자의 성별, 나이, 병동, 기저질환, 이전의 항생제 사용력, 패혈증 발생당시까지의 재원기간, 이전 입원력, 원인균의ESBL 생성유무 등을 파악하였고 이들 변수가 ciprofloxacin 내성과 관련이 있는지를 분석하였다. 재발성 패혈증의 경우는 첫 번째 경우만을 분석에 포함하였다. 결과 : 연구대상 환자는 총154명이었고 K. pneumoniae의 ciprofloxacin에 대한 내성률은 28.6% (44/154)였다. Ciprofloxacin 내성균주 중 ESBL 생성균주의 비율은 95.5% (42/44)였고 ciprofloxacin 감수성균주에서 ESBL 생성균주의 비율은 24.5% (27/110)였다(P<0.001). ESBL생성외에 단변량 분석에서 유의한 관련을 보인 변수로는 남자, 나이가 많은 경우, 패혈증 당시 중환자실 재원, 기저질환이 고형암, 혈액암, 담도계 질환인 경우, 패혈증 발생이전 1달 이내의 항생제 사용력, 3세대 cephalosporin, metronidazole, fluroquinolone, carbapenem 투여력이 있었다. 다변량 로지스틱 분석을 시행 하였을 때는 나이가 많은 경우(Adjusted odds ratio[A0R]; 1.04, 95%confidence interval[CI]; 1.01-1.06)와 ESBL 생성(AOR; 81.35, 95% CI; 17.76-372.53)이 유의하게 ciprofloxacin 내성과 관련이 있었다. 결론 : 패혈증을 일으킨 병원획득 K. pneumonias에서의 ciprofloxacin 내성은 ESBL 생성과 유의한 관련을 보였고 향후 이에 관련된 원인이나 기전을 분석하기위한 분자역학적·분자생물학적 연구가 필요하겠다. Background : Strains of ciprofloxacin-resistant Klebsiella pneumoniae have emerged worldwide. We investigated the epidemiology of ciprofloxacin resistance and its relationship to ESBL production in nosocomial K. pneumoniae bacteremia. Materials and Methods : Using the computerized database of clinical microbiology, we identified all patients whose blood culture had yielded K. pneumoniae between January 2001 and December 2002 at a 2200-bed university-affiliated tertiary-care hospital. During the study period, total of 392 episodes of K. pneumoniae bacteremia were documented of which 163 episodes were acquired nosocomially. 9 cases of recurrent episodes were excluded. Results : The resistance rates to ciprofloxacin was 28.6% (44/154). ESBL-production was significantly more common in ciprofloxacin-resistant isolates than in ciprofloxacin-susceptible isolates (95.9% [42/44] vs. 24.5% [27/110], P<0.001). In univariate analysis, following factors were significantly associated with resistance to ciprofloxacin: older age, male sex, ICU admission at the time of bacteremia, prior use of antibiotics within 1 month before bacteremia, solid tumor, hematological malignancy, or biliary disease as underlying disease, and ESBL-production. The prior use of 3^(rd)-generation cephalosprins, metronidazole, fluroquinolone, or carbapenem were also risk factors. Independent risk factors for ciprofloxacin resistance were older age (adjusted odds ratio [AOR]; 1.04, 95% confidence interval [CI]; 1.01-1.06) and ESBL production (AOR; 81.35, 95% CI; 17.76-372.53). Conclusion : The close relationship between ciprofloxacin resistance and ESBL production was documented in nosocomial K. pneumoniae bacteremia. Further epidemiological and molecular studies to determine factors and mechanisms involved in the relationship are needed.

A case of dermatomyositis with interstitial pneumonitis complicated with pneumomediastinum successfully improved on cyclosporin A

( Seong Su Nah ),( Kyung Hoon Lee ),( Chang Hee Jung ),( Jung Ho Bae ),( Se Hee Kim ),( Chang Keun Lee ),( Dong Sun Kim ),( Bin Yoo ) 대한내과학회 2005 대한내과학회 추계학술대회 Vol.69 No.10

Epidermal growth factor increases prostaglandin E2 production via ERK1/2 MAPK and NF-κB pathway in fibroblast like synoviocytes from patients with rheumatoid arthritis

Nah, Seong-Su,Won, Hye-Jin,Ha, Eunyoung,Kang, Insug,Cho, Hong Yon,Hur, Sook-Jin,Lee, Sang-Hoon,Baik, Hyung Hwan Springer-Verlag 2010 Rheumatology international Vol.30 No.4

Association of Guanosine Triphosphate Cyclohydrolase 1 Gene Polymorphisms with Fibromyalgia Syndrome in a Korean Population

KIM, SEONG-KYU,KIM, SEONG-HO,NAH, SEONG-SU,LEE, JI HYUN,HONG, SEUNG-JAE,KIM, HYUN-SOOK,LEE, HYE-SOON,KIM, HYOUN AH,JOUNG, CHUNG-IL,BAE, JISUK,CHOE, JUNG-YOON,LEE, SHIN-SEOK Journal of Rheumatology 2013 The Journal of rheumatology Vol.40 No.3

<P><B>Objective.</B></P><P>Guanosine triphosphate cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the synthesis of tetrahydrobiopterin, which is an essential cofactor in nitric oxide (NO) production. Polymorphisms in the <I>GCH1</I> gene have been implicated in protection against pain sensitivity. The aim of our study was to determine whether single-nucleotide polymorphisms (SNP) in the <I>GCH1</I> gene affect susceptibility and/or pain sensitivity in fibromyalgia syndrome (FM).</P><P><B>Methods.</B></P><P>A total of 409 patients with FM and 422 controls were enrolled. The alleles and genotypes at 4 positions [rs3783641(T>A), rs841(C>T), rs752688(C>T), and rs4411417(T>C)] in the <I>GCH1</I> gene were analyzed. The associations of the <I>GCH1</I> SNP with susceptibility and clinical measures in patients with FM were assessed.</P><P><B>Results.</B></P><P>The frequencies of alleles and genotypes of the 4 SNP did not differ between patients with FM and healthy controls. Among 13 constructed haplotypes, we further examined 4 (CCTT, TTCT, TTCA, and CCTA) with > 1% frequency in both FM and controls. No associations of <I>GCH1</I> polymorphisms with FM-related activity or severity indexes were found, although the number and total score of tender points in patients with FM differed among the 4 haplotypes (p = 0.03 and p = 0.01, respectively). The CCTA haplotype of <I>GCH1</I> was associated with significantly lower pain sensitivity and occurred less frequently than the CCTT haplotype in patients with FM (p = 0.04, OR 0.45, 95% CI 0.21–0.96).</P><P><B>Conclusion.</B></P><P>Our study provides evidence that certain <I>GCH1</I> haplotypes may be protective against susceptibility and pain sensitivity in FM. Our data suggest that NO is responsible for pain sensitivity in the pathogenesis of FM.</P>

골관절염 연골세포에서 진행성당화종말생성물에 의한 기질단백분해효소 발현의 증가

나성수 ( Seong Su Nah ),최인영 ( In Young Choi ),문세환 ( Se Hwan Mun ),김용길 ( Yong Gil Kim ),문희범 ( Hee Bom Moon ),유빈 ( Bin Yoo ),이창근 ( Chang Keun Lee ) 대한류마티스학회 2007 대한류마티스학회지 Vol.14 No.1

Objective: Although increased expression of receptor for advanced glycation end products (AGE) in osteoarthritis (OA) has been reported, little is known concerning the role of AGEs in the pathogenesis of OA. This study was undertaken to determine the effect of AGEs on the regulation of matrix metalloproteinase (MMP) expressions and activities in human OA chondrocytes Methods: OA chondrocytes were treated with increasing doses of AGE-bovine serum albumin (AGE-BSA). The expressions of MMPs were determined by both enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. The activities of MMPs were evaluated by both gelatin and casein zymography assays. In addition, electrophoretic mobility shift assay (EMSA) was employed to investigate the DNA binding activity of nuclear factor-kappa B (NF-κB) by AGE-BSA treatment. Results: The productions of MMP-1, -3, and -13 were significantly elevated by AGE-BSA in a dose dependent manner. The elevated activities of MMP-1, -3, and -13, and TNF-α by AGE-BSA were also observed. DNA binding activity of NF-κB was markedly increased by AGE-BSA treatment implicating possible involvement of NF-κB mediated pathway in the AGE-BSA induced MMP-1, -3, and -13, and TNF-α productions in OA chondrocytes. Taken together, this study demonstrates the stimulatory effect of AGE-BSA on the productions of MMPs and TNF-α and suggests the possible involvement of NF-κB mediated pathway in OA chondrocytes. Conclusion: These results suggest that AGE may play a role in pathogenesis of OA.

베체트병의 심혈관 침범 환자의 재발에서 면역억제제의 효과

나성수 ( Seong Su Nah ),이창근 ( Chang Keun Lee ),오지선 ( Ji Seon Oh ),김용길 ( Yong Gil Kim ),전찬홍 ( Chan Hong Jeon ),문희범 ( Hee Bom Moon ),고은미 ( Eun Mi Koh ),유빈 ( Bin Yoo ),홍석찬 ( Seok Chan Hong ) 대한류마티스학회 2007 대한류마티스학회지 Vol.14 No.4

Objective: Despite the high risk for disease-related morbidity and mortality in Behcet`s disease (BD) with cardiovascular (CV) manifestations, only a few studies concerning BD with CV involvements are available. We conducted study to evaluate the clinical manifestations of CV BD (cardiovascular Behcet`s disease) and the clinical outcome according to the different treatment modalities, especially focusing on the immunosuppressive agents. Methods: We retrospectively reviewed 1,812 patients diagnosed with BD at tertiary hospital. All patients with vascular involvements were classified into three groups by lesion site. We assessed clinical characteristics, treatments, outcome and recurrence in each group. Results: Of 1,812 patients, 79 patients showed CV involvements. Male to female ratio was 65 (82.3%) to 14 (17.7%). Venous involvements occurred in 57 cases (72.2%), arterial lesions in 22 (27.8%), cardiac involvements 16 (20.3%). In clinical manifestation, only hypertension and arthritis were more frequently found in cardiac lesion than in venous lesion (p=0.01, p=0.01, respectively). CV lesions recurred in 16 patients (20.3%), mostly at the same sites as previous involvements. There was no association of recurrence with site of lesion (p=0.49). Recurrent rate was significant different in three medication group (p=0.028). Recurrences were more frequent in patients treated with no immunosuppressive agent and colchicines only or colchicines with prednisolone than in patients treated with additional immunosuppressive agent (p=0.024, R.R, 7.16 (95% CI, 1.55 to 32.99)). Conclusion: Recurrence rate was lower in patients with aggressive immunosuppressive treatment. Although most of patients improved, more efforts to decrease the relatively high rate of the recurrence (20.3%) would be needed.

Sensitive detection method of Foot-and-mouth disease virus in pigs by oral-fluid using cotton rope

Tae seong Kim,So yoon Ryoo,Jin ju Nah,Min geun Sagong,Su mee Lee,Ki Sik Choung,Sung Hwan Wee,Bok Kyung Ku 대한수의학회 2016 대한수의학회 학술대회발표집 Vol.2016 No.-

PER2 is downregulated by the LPS-induced inflammatory response in synoviocytes in rheumatoid arthritis and is implicated in disease susceptibility

Lee, Hwayoung,Nah, Seong-Su,Chang, Sung-Hae,Kim, Hyung-Ki,Kwon, Jun-Tack,Lee, Sanghyun,Cho, Ik-Hyun,Lee, Sang Won,Kim, Young Ock,Hong, Seung-Jae,Kim, Hak-Jae SPANDIDOS PUBLICATIONS 2017 MOLECULAR MEDICINE REPORTS Vol. No.

<P>The clinical symptoms of rheumatoid arthritis (RA) present with circadian variation, with joint stiffness and pain more prominent in the early morning. The mammalian clock genes, which include circadian locomotor output cycles kaput, brain and muscle Arnt-like protein 1, period and cryptochrome, regulate circadian rhythms. In order to identify the association between genetic polymorphisms in the circadian clock gene period 2 (PER2) and RA, the present study genotyped three PER2 single nucleotide polymorphisms (SNPs), rs934945, rs6754875, and rs2304674, using genetic information from 256 RA patients and 499 control subjects. Primary cultured rheumatoid synovial cells were stimulated with 10 mu M lipopolysaccharide (LPS). Total protein was then extracted from the synovial cells following 12 and 24 h, and PER2 protein expression was assayed by immunoblotting. The rs2304674 SNP demonstrated a significant association with susceptibility to RA following Bonferroni correction. However, statistical analysis indicated that the SNPs were not associated with any clinical features of patients with RA. Immunoblotting analysis demonstrated that PER2 protein expression was decreased by LPS-induced inflammation in RA synovial cells; however, this was not observed in normal synovial cells. The results suggest that the PER2 gene may be a risk factor for RA, and expression of the PER2 protein may be affected by inflammation. Therefore, PER2 may contribute to the pathogenesis of RA.</P>

A study on consistency and accuracy of pulse diagnosis in Eight-Constitution Medicine

Shin, Yong-Sup,Nah, Seong-Su,Oh, Hwan-Sup,Park, Young-Jae,Park, Young-Bae Kyung Hee Oriental Medicine Research Center 2009 Oriental pharmacy and experimental medicine Vol.9 No.1

The aim of this study is to evaluate appraiser's consistency and accuracy about pulse diagnosis (PD) in discrimination of eight-constitutions using Gage R&R study. Cumulative numbers of PD for discrimination of eight constitutions of three appraisers' experience were 75,000 cases, 50,000 cases, 1,100 cases, respectively. Three Appraisers diagnosed subject's eight-constitutions by PD with blinded method. Gage R&R study was used to verify the results. In the measurements of consistency, appraiser B (agreement = 80%, Value of k = 0.8276) was very good, appraiser A (agreement = 70%, Value of k = 0.7465) was good, and appraiser C (agreement = 50%, Value of k = 0.5365) was moderate. In the measurements of accuracy, appraiser B (agreement = 70%, Value of k = 0.6812) was good, appraiser A (agreement = 60%, Value of k = 0.6414) was good, and appraiser C (agreement = 0%, Value of k = -0.1000) was poor. The results suggest that accuracy of discrimination of constitutions relatively depend on experience and number of cases of PD. Further large controlled study is needed to evaluate the accuracy of PD.

Tumor necrosis factor α–induced interleukin-32 is positively regulated via the Syk/protein kinase Cδ/JNK pathway in rheumatoid synovial fibroblasts

Mun, Se Hwan,Kim, Jie Wan,Nah, Seong Su,Ko, Na Young,Lee, Jun Ho,Kim, Ju Dong,Kim, Do Kyun,Kim, Hyuk Soon,Choi, Ji Da,Kim, Soo Hyun,Lee, Chang Keun,Park, Seung Hwa,Kim, Bo Kyung,Kim, Hyung Sik,Kim, Yo Wiley Subscription Services, Inc., A Wiley Company 2009 Vol.60 No.3

<B>Objective</B><P>Interleukin-32 (IL-32) is a recently discovered cytokine that appears to play a critical role in human rheumatoid arthritis (RA). It is highly expressed in synovium and fibroblast-like synoviocytes (FLS) from RA patients, but not in patients with osteoarthritis (OA). This study was undertaken to assess IL-32 levels in RA synovial fluid (SF) and to investigate the secretion and regulation of IL-32 in RA FLS.</P><B>Methods</B><P>FLS and SF were obtained from the joints of RA patients. The secretion and expression of IL-32 and activation of signaling molecules were examined by enzyme-linked immunosorbent assay, immunoblotting, immunoprecipitation, reverse transcriptase–polymerase chain reaction, and small interfering RNA (siRNA) transfection.</P><B>Results</B><P>IL-32 levels were high in RA SF compared with OA SF. Furthermore, RA FLS expressed and secreted IL-32 when stimulated with tumor necrosis factor α (TNFα). TNFα-induced expression of IL-32 was significantly suppressed, in a dose-dependent manner, by inhibitors of Syk, protein kinase Cδ (PKCδ), and JNK and by knockdown of these kinases and c-Jun with siRNA. We also observed that PKCδ mediated the activation of JNK and c-Jun, and experiments using specific inhibitors and siRNA demonstrated that Syk was the upstream kinase for the activation of PKCδ.</P><B>Conclusion</B><P>The present findings suggest that IL-32 may be a newly identified prognostic biomarker in RA, thereby adding valuable knowledge to the understanding of this disease. The results also demonstrate that the production of IL-32 in RA FLS is regulated by Syk/PKCδ-mediated signaling events.</P>