7개 대학 병원에서 조사한 지역사회 폐렴의 원인균

정문현,김성민,강문원,최희정,정희진,이경원,한성우,송재훈,신형식,김의종,최강원,김민자,박승철,배현주,정윤섭,김준명,백경란,신완식,이규만,김양리 대한감염학회 1997 감염 Vol.29 No.5

목 적 : 폐렴은 많이 발생하면서 사망률이 크게 줄지 않는 질환이며, 이를 적절히 치료하기 위해서는 원인균의 상대적 빈도, 기저 질환에 따른 변화, 항균제 내성률, 사망에 관련된 인자들을 알아야 한다. 원인균의 빈도는 지역마다 차이가 있고 국내에서는 항균제 내성률이 높아 지역사회에서 발생한 폐렴을 치료하기 위한 경험적 항균제 선택에 도움이 되기 위해 서울 소재 6개 대학 병원과 천안의 1개 대학 병원이 참여하여 위의 사항들에 대해 조사를 하였다. 방 법 : 1995년에 내과에 입원했던 16세 이상 환자를 대상으로 했다. 퇴원 진단명이 폐렴 또는 폐결핵인 병록지을 찾았고, 이중에서 병원 감염을 제외하였다. 특이도를 높이기 위해, 이들 중에서 호흡기 증상이 있고 발열이나 저체온이 있으면서 흉부 X-선에서 이상 음영이 있는 환자만을 대상으로 했다. 폐결핵은 위의 기준에 입원 초기에 항균제 치료를 하고 입원 7일 이후에야 항결핵제가 투여된 경우만을 폐렴의 원인균으로 하였다. 혈액 배양에서 양성, 객담에서 항상균이나 M. tuberculosis가 증명된 경우, 혈청학적으로 항체가가 4배 이상 증가된 경우, 조직에서 원인균이 진단된 경우는 확정(definitive) 원인균으로 하였고, 객담에서 배양된 균이 그람 도말과 일치할때, 항결액제에 대한 반응으로 진단한 폐결핵, 단일 항체가 양성이고 이에 대해 항균제를 사용했을 때는 가능(probable) 원인균으로 정의하였다. 다세균 감염균은 각각 다 른 원인균으로 처리하였다. 임상 조사와 함께 임상병리과에서 S. pneumoniae, H. influenzae, M. catarrhalis, mycoplasma, 항상균에 대해 검사 의뢰 건수, 배양 양성수, 항균제 감수성 결과를 조사하였다. 결 과 : 폐렴의 증례 정의에 부합하지 않은 135명과 폐결핵의 정의에 해당하지 않는 230명을 제외하고 남은 246명의 평균 나이는 58.2세이고 남성이 142명(58.2%) 이었고, 71%의 환자에서 기저 질환이 있었다. 진단 방법의 시행 횟수는 혈액 배양 77.6%, 혈청 검사 18.3%, 기관지경 검사는 4.1%였고, 세균의 항원 검사를 한 예는 없었다. 원인균이 밝혀진 예는 77명(31.3%)이었다. 다세균 감염이 4명에서 있었고, 원인균의 상대적 빈도는 결핵 20명(확정 17, 가능 3: 6개 병원 자료), 폐렴구균 18(확정8 가능 10)명과 폐렴구균이 아닌 Streptococcus 3명 (모두 확정), H. influenzae 11명(모두 가능), 그람음성간균 11명(확정 7, 가능 4) (K. pneumoniae 8건), Mycoplasma 5명(확정 1, 가능 4), S. aureus 4명(확정 2, 가능 2), mucormycosis 1명(확정)이었다. 평균 입원 기간은 19일이고, 중환자실 입원률과 인공 호흡기 사용율은 각각 18%와 9.3%였다. 사망률은 13.8%였고 사망까지 평균 기간은 14.6일 이었다. 다변량 분석에서 사망을 예측할 수 있는 인자는 저체온과 빈호흡이었다. 임상병리과에서 배양되었던 모든 폐렴구균의 Penicillin 내성률은 서울 3개 병원에서 82-88%, 천안에서 72%였다. 폐렴 환자의 혈액에서 배양된 7주는 모두 Penicillin에 감수성이 있었다. K. pneumoniae 8주 모두 cefotaxime과 gentamicin에 감수성을 보였다. 결 론 : 후향적 조사이고 병원마다 원인균 진단에 차이가 있지만, 원인이 밝혀진 경우에는 결핵과 폐렴균이 흔하였고, 무균 부위에서 배양된 폐렴구균의 항균제 내성률은 낮았다. 원인이 밝혀지지 않은 경우가 많고, 혈청검사로 진단되는 원인균이 드물며, 분리균주가 적어 항균제 내성 정도를 추정하기 어려워, 이를 밝히기 위한 전향적 조사가 필요하다. Background : Community-acquired pneumonia (CAP) is one of the leading causes of mortality and morbidity, but its management is still challenging. The limitation of diagnostic methods to identify etiologic agents rapidly make it necessary to use empiric antibiotics in almost all patients, and furthermore the discovery of new respiratory pathogens and the emergence of antibiotic-resistant organisms pose difficulties to the selection of an empiric regimen. To clarify the factors necessary for the optimal choice of empirical antibiotics, such as the frequency of etiologic agents, the attributable rates to death and antimicrobial resistance rates in the community, six university hospitals in Seoul and one university hospital in Cheonan were participating in this study. Methods : medical records of adults (>15 years of age) hospitalized for CAP or pulmonary tuberculosis between April 1995 and March 1996, were reviewed. Patients who satisfied all of the following criteria were included in the study: (1) fever or hypothermia; (2) respiratory symptoms; and (3) pulmonary infiltrates on chest roentgenogram. To exclude cases of pulmonary tuberculosis whose roentgenographic features were so typical that it could be easily differentiated from conventional pneumonia, two additional criteria were required for inclusion: antibiotic treatment during the first week of hospital admission and initiation of anti-tuberculosis medications thereafter. Organisms isolated from sterile body sites, acid-fast bacilli or Mycobacterium tuberculosis isolated from sputum, pathogens diagnosed by a 4-fold rising titer of antibodies to “atypical”pathogens, or pathogens revealed by histopathology were defined as definitive cause of pneumonia; isolates from sputum withcompatible Gram stain, pathogens diagnosed by a single diagnostic titer plus use of a specific antimicrobial agent, or tuberculosis diagnosed by clinucal response to anti- tuberculosis medications were considered probable cause of pneumonia. The records of the clinical microbiology were reviewed for isolates of S. pneumoniae, H. influenzae, M. catarrhalis, Mycobacterium or acid-fast bacilli, and Mycoplasma. Then the frequency of these agents, antimicrobial resistance rates of resiratory pathogens from all body sites, and their clinical significance were evaluated. Results: After excluding 365 patients (230 with pulmonary tuberculosis and 135 with CAP) who were screened for inclusion but did not meet the inclusion criteria,246 persons were enrolled in this study. Their mean age was 58.2 years old with slight male predominance (58.2%), and 171(71%) patients had underlying illnesses. Blood cultures were performed on 191 (77.6%) patients and serologic tests on 44(18.3%) patients. The etiologic agents were identified in 31.3%, and the list of individual agents, in decreasing order, was pulmonary tuberculosis (17 definite and 3 probable: data of six hospitals), S. pneumoniae (8 definite and 10 probable), non-pneumococci (3 definite), aerobic gram-negative bacilli (7 definite and 4 probable), Haemophilus spp. (11 probable), mycoplasma (1 definite and 4 probable), polymicrobial infections (2 definite and 2 probable: E. coli and S. agalactiae, M. tuberculosis and S. aureus, S. pneumoniae and H. influenzae and A. baumannii and K. pneumonias), S. aureus (2 definite and 2 probable) , and mucormycosis (1 definite). Among gram-negative bacilli, K. pneumoniae was the most common agent (8isolates). therates of admission to the intensive care unitand of using assisted ventilation were 18% and 9.3%, respectively. The mortality was 13.8% and logistic regression analysis showed that hypothermia and tachypnea were associated with death. Hospital stay averaged 19 days. Susceptible rates of S. pneumoniae isolated from all body sites to penicillin ranged from 8% to 28% but seven isolated from blood of patients with pneumonia were susceptible to penicillin. Also all 8 isolated of k> pneumoniae from patients with pneumonia were susceptible to cefotaxime and gentamicin. Conclusion: In Korea, in addition to S. pneumoniae, M. tuberculosis is an important agent causing community-acquired pneumonia. The low incidence of etiologic diagnosis is probably related to infrequent requesting of test "atypical" pathogens and does not represent the true incidence of infections by "atypical" pathogens, which well be answered by a prospective study. The antimicrobial resistance rates of major respiratory pathogens from sterile body sites are low, however, because of a small number of the isolates this result needs confirmation by a nationwide surveillance of antimicrobial resistance.

Distribution and Potential Toxicological Effects of 2,2',4,4'-tetrabromodiphenyl Ether (BDE-47) as a Endocrine Disrupting Chemical in Human and Animals

Jung, Eui-Man,Yang, Hyun,An, Beum-Soo,Lee, Geun-Shik,Hyun, Sang-Hwan,Choi, Kyung-Chul,Jeung, Eui-Bae 韓國受精卵移植學會 2011 한국동물생명공학회지 Vol.26 No.4

Polybrominated diphenyl ethers (PBDEs) are a class of "brominated" (bromine containing) man-made chemicals used as flame retardant additives in plastics, foams, and textiles. PBDEs are found in various environmental contaminants in air, soil, sediment, and water, and 209 individual forms (congeners) of PBDE exist. Among these, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is the dominant congener found in the environment. Exposure to BDE-47 is now worldwide, and levels of BDE-47 have been detected in the blood of animals, including humans. BDE-47 can adversely affect the developmental system in both humans and animals. BDEs have structural similarities to polychlorinated biphenyls and thyroid hormones. However, recent studies have shown that BDEs may act as hormonal disrupting chemicals with detrimental effects. Therefore, a reliable assessment of BDE-47 toxicological action is required to understand the detrimental impacts of BDE-47 on human health. In this review, we overview recent studies on the distribution and potential toxicological effects of BDE-47 in humans and animals.

유전자 재조합에 의해 제조된 하루딘의 항응고 작용

정기화,김영식,이상기,손정훈,최의성,엄은미,정정숙,정춘식 한국응용약물학회 1993 Biomolecules & Therapeutics(구 응용약물학회지) Vol.1 No.2

Hirudin is a potent inhibitor of thrombin, which was originally obtained from the medicinal leech (Hirudo medicinalis). Now it is being produced through the recombinant technology on a large scale. Recombinant hirudin has been assayed for the anticoagulant activity by the measurement of clotting time and the inhibition of thrombin actvity using a chromogenic substrate. The assay range of partial thromboplastin time and thrombin time is within 0.2∼1.0 ,㎍/㎖. Thrombin time is more sensitive to the measurement of clot. Ex vivo study showed the level of hirudin in rat plasma was highest in 10 min and then it was eliminated slowly. The half-life of r-hirudin was 80∼110 min depending on the assay methods. Intraveneous injection of russel viper venom was used for thrombus induction combined with vena cava ligation. Inhibition of venous thrombosis was observed with i.v. hirudin. It was dependent on the concentration of hirudin.

Establishment of inducible cAMP early repressor transgenic fibroblasts in a porcine model of human type 1 diabetes mellitus.

Jung, Eui-Man,Kim, Yu-Kyung,Lee, Geun-Shik,Hyun, Sang-Hwan,Hwang, Woo-Suk,Jeung, Eui-Bae D. A. Spandidos 2012 MOLECULAR MEDICINE REPORTS Vol.6 No.1

<P>Diabetes mellitus is a metabolic disease caused by impaired insulin secretion from the pancreatic β cells and increased insulin resistance in peripheral tissues. Recently, the overexpression of inducible cyclic AMP (cAMP) early repressor (ICER) Iγ in rodent pancreatic β cells was found to induce insulin deficiency and glucagon overproduction similar to that found in human diabetes mellitus. ICER Iγ with only a DNA binding domain interrupts the transcriptional regulation of the cAMP responsive element-binding protein (CREB) target genes. Based on this information, we hypothesized that the overexpression of ICER Iγ, the most powerful competitor to CREB, could be useful for generating a pig model of diabetes. First, we evaluated the promoter activities of the human insulin gene for the β cell-specific overexpression of ICER Iγ in the pig pancreas. The maximum promoter activity region [-1,431 nucleotides (nt) to +1 nt, +1 = the transcriptional start site] of the insulin gene presented an activity level 3-fold higher than a promoterless construct. Second, ICER Iγ overexpression controlled by this promoter region significantly blocked the glucose-mediated insulin transcription, such as that regulated by the viral promoter in the pancreatic β?cell line, MIN6. This suggests that the human insulin promoter may facilitate the overexpression of ICER?Iγ in porcine pancreatic β cells. In addition, the overexpression of ICER?Iγ in porcine β cells may induce human-like type 1 diabetes mellitus in pigs. In the present study, we generated transgenic fibroblasts containing ICER Iγ cDNA controlled by the human insulin promoter, as well as two screening markers, the green fluorescence protein and the neomycin resistance gene. These fibroblasts may provide a source for somatic cell nuclear transfer to generate a pig model that mimics human diabetes mellitus.</P>

Protective effects of Korean Red Ginseng against toxicity of endocrine-disrupting chemicals

Eui-Man Jung,Seung Hyun Lee,Geun-Shik Lee The Korean Society of Ginseng 2023 Journal of Ginseng Research Vol.47 No.2

Several chemicals have been developed owing to the progression of industrialization, among which endocrine-disrupting chemicals (EDCs; essential for plastic production) are used as plasticizers and flame retardants. Plastics have become an essential element in modern life because they provide convenience, thus increasing EDCs exposure to humans. EDCs cause adverse effects such as deterioration of reproductive function, cancer, and neurological abnormalities by disrupting the endocrine system and hence are classified as "dangerous substances." Additionally, they are toxic to various organs but continue to be used. Therefore, it is necessary to review the contamination status of EDCs, select potentially hazardous substances for management, and monitor the safety standards. In addition, it is necessary to discover substances that can protect against EDC toxicity and conduct active research on the protective effects of these substances. According to recent research, Korean Red Ginseng (KRG) exhibits protective effects against several toxicities caused by EDCs to humans. In this review, the effects of EDCs on the human body and the role of KRG in protection against EDC toxicity are discussed.

Integrin-Linked Kinase Controls Notch1 Signaling by Down-Regulation of Protein Stability through Fbw7 Ubiquitin Ligase

Mo, Jung-Soon,Kim, Mi-Yeon,Han, Seung-Ok,Kim, In-Sook,Ann, Eun-Jung,Lee, Kyu Shik,Seo, Mi-Sun,Kim, Jin-Young,Lee, Seung-Chul,Park, Jeen-Woo,Choi, Eui-Ju,Seong, Jae Young,Joe, Cheol O.,Faessler, Reinha American Society for Microbiology 2007 Molecular and cellular biology Vol.27 No.15

<B>ABSTRACT</B><P>Integrin-linked kinase (ILK) is a scaffold and protein kinase that acts as a pivotal effector in integrin signaling for various cellular functions. In this study, we found that ILK remarkably reduced the protein stability of Notch1 through Fbw7. The kinase activity of ILK was essential for the inhibition of Notch1 signaling. Notably, the protein level and transcriptional activity of the endogenous Notch1 intracellular domain (Notch1-IC) were higher in ILK-null cells than in ILK wild-type cells, and the level of endogenous Notch1-IC was increased by the blocking of the proteasome, suggesting that ILK enhances the proteasomal degradation of Notch1-IC. ILK directly bound and phosphorylated Notch1-IC, thereby facilitating proteasomal protein degradation through Fbw7. Furthermore, we found down-regulation of Notch1-IC and up-regulation of ILK in basal cell carcinoma and melanoma patients but not in squamous cell carcinoma patients. These results suggest that ILK down-regulated the protein stability of Notch1-IC through the ubiquitin-proteasome pathway by means of Fbw7.</P>

Estrogen Receptor α Pathway Is Involved in the Regulation of <i>Calbindin-D_9k</i> in the Uterus of Immature Rats

Lee, Geun-Shik,Kim, Hoe-Jin,Jung, Yong-Woo,Choi, Kyung-Chul,Jeung, Eui-Bae Oxford University Press 2005 TOXICOLOGICAL SCIENCES Vol.84 No.2

<P>It has been demonstrated in our previous studies that <I>Calbindin-D<SUB>9k</SUB></I> (<I>CaBP-9k</I>) is a potent biomarker for screening estrogen-like chemicals in the rat model. Although treatments with 17beta-estradiol (E2) and endocrine disrupting compounds resulted in the up-regulation of uterine CaBP-9k, the mechanism of <I>CaBP-9k</I> induction by these compounds through two subtypes of estrogen receptors (ERα and ERβ) is unclear. Thus, in the present study, immature rats were treated with propyl pyrazole triol (PPT, an ERα-selective ligand), diarylpropionitrile (DPN, an ERβ-selective ligand), E2, or dimethyl sulfoxide (DMSO, a vehicle control) for three days in order to clarify which subtype of ER is involved in the uterine <I>CaBP-9k</I> induction. Following injection with these ER ligands, uterine <I>CaBP-9k</I> expression was analyzed by Northern blot and immunoblot assays. Uterine <I>CaBP-9k</I> expression is mainly mediated by PPT in a dose- and time-dependent manner in immature rats, whereas no significant alteration of the uterine <I>CaBP-9k</I> gene was observed after DPN treatment. In addition, an estrogenicity of PPT in inducing <I>CaBP-9k</I> expression was completely blocked by the anti-estrogen ICI 182,780, implying that uterine <I>CaBP-9k</I> is solely induced by ERα. A single treatment with PPT rapidly increased the protein levels of ERα and PR, an E2-mediated gene, in these tissues. Taken together, these results indicate that uterine <I>CaBP-9k</I> is induced by E2 and endocrine disrupting chemicals via the ERα pathway, but not ERβ, in the uterus of immature rats.</P>

Compensatory induction of the TRPV6 channel in a calbindin-D9k knockout mouse: Its regulation by 1,25-hydroxyvitamin D₃

Lee, Geun-Shik,Jung, Eui-Man,Choi, Kyung-Chul,Oh, Goo Taeg,Jeung, Eui-Bae Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of cellular biochemistry Vol.108 No.5

<P>Active calcium transport is carried out by calcium channel proteins, cytosolic buffering or transfer proteins, and pump proteins. Several components of this transport system have recently been verified using gene knockout (KO) models. We previously generated calbindin-D9k (CaBP-9k) KO mice and reported that induction of expression of some calcium transport proteins can compensate for the CaBP-9k gene deficiency. In the current study, we have further clarified the compensatory regulation of calcium transport genes by two calcium regulating hormones, 1,25-dihydroxyvitamin D<SUB>3</SUB> (1,25(OH)<SUB>2</SUB>D<SUB>3</SUB>) and parathyroid hormone (PTH), in CaBP-9k KO mice, because the levels of these hormones differ between the KO and wild-type (WT) mice. The induction of transient receptor potential cation channel, subfamily V, member 6 (TRPV6) in the duodenum was observed in adult KO male mice but induction was not modified by physiologic doses of 1,25(OH)<SUB>2</SUB>D<SUB>3</SUB>. Duodenal TRPV6 transcription in WT and female KO mice were modulated by 1,25(OH)<SUB>2</SUB>D<SUB>3</SUB> in a dose-dependent manner. This compensatory gene induction was not detected in the mice fed a vitamin D<SUB>3</SUB>-deficient diet. Compensatory gene induction was not affected by PTH. Thus, the compensatory expression of duodenal TRPV6 in the KO male mice may be tightly correlated with serum 1,25(OH)<SUB>2</SUB>D<SUB>3</SUB>. Vitamin D receptor (VDR) transcription and protein levels were measured to examine whether VDR expression mediates differential regulation of duodenal TRPV6 between WT and KO mice, but expression and levels of VDR were similar in both genotypes. The compensatory TRPV6 transcripts in KO mice may be modulated by endogenous vitamin D<SUB>3</SUB> via other factors of VDR signaling complexes. J. Cell. Biochem. 108: 1175–1183, 2009. © 2009 Wiley-Liss, Inc.</P>

장기 이식 환자에서 인형 거대세포바이러스(Human Cytomegalovirus) 감염에 관한 연구

최희정,김병국,김의종,신형식,최강원,박선양,김상준,오명돈 대한감염학회 1997 감염 Vol.29 No.1

배경: HCMV는 일차 감염후 잠복 감염 상태로 있으면서 숙주의 면역능이 떨어지면 재발 감염을 일으킨다. 우리나라 성인 인구의 HCMV에 의한 일차 감염률은 95% 이상으로 높아, 이식 환자에서 HCMV에 의한 감염의 빈도가 높을 것으로 예상된다. 방법: 골수 이식환자 14명, 신 이식환자 44명 그리고 간 이식환자 4명을 대상으로 이식전과 이식후에 전통적인 바이러스 배양법으로 소변과 혈액에서 HCMV를 분리하였다. 또한 이식 환자 41명에서 shell vial assay를 이용하여 HCMV를 검출하고, 그 성적을 전통적인 배양법에 의한 성적과 비교하여 민감도와 특이도를 평가하였다. 성적: HCMV 감염의 빈도는 골수 이식 환자의 경우 50%(7/14), 신이식 환자 36%(16/44), 간이식 환자 25%(1/4)였다. HCMV 질환으로 골수 이식 환자 3명에게 간질성 폐렴이 관찰되었다. Shell vial assay 법을 이용한 HCMV 검출의 민감도는 50%(3/6), 특이도는 91%(32/35)였다. 결론: 국내 이식 환자에서 HCMV에 의한 감염은 비교적 흔히 발생하며, 이식 1개월이후에는 그 발생빈도가 33-50%로 높다. Shell vial assay법은 민감도가 낮아 다른 진단법과 상호 보완해서 시행하는 것이 바람직하다고 생각된다. Background: Human cytomegalovirus(HCMV) is not eradicated from a host after a primary infection and persists in a latent form. When the immunological condition of the host is compromised, the virus can be reactivated and cause serious disease. Given that the prevalence of anti-HCMV IgG antibody positivity is over 95% in Korean adult population, the transplant recipients in Korea are likely to be a high risk of developing HCMV infection and diseases. Methods: Fourteen bone marrow recipients, 44 kidney transplant recipients and 4 liver transplant recipients were evaluated for excretion of HCMV. Urine and blood were cultured by conventional method at the time of transplantation and at regular intervals thereafter. To evaluate sensitivity and specificity of shell vial assay for detecting HCMV, the specimens from 41 transplant recipients were cultured by using both shell vial assay and conventional virus culture. Results: The frequency of HCMV infection was 50%(7/14) in allogeneic bone marrow(BM) recipients, 36%(16/44) in kidney recipients and 25%(1/4) in liver transplant recipients. HCMV diseases were observed in only 3 cases; 3 BM recipients developed interstitial pneumonitis. Sensitivity and specificity of shell vial assay for the detection of HCMV was 50%(3/6) and 91%(32/35), respectively. Conclusion: HCMV infections in organ transplant recipients were relatively common in Korea. HCMV started to be excreted in urine about 1 month after transplantation and were found in 33-50% of all recipients later on. Sensitivity of shell vial assay was so low that it need to be complemented with other diagnostic methods.

유도의 선택된 메치기 기술 발휘시 매트반력에 관한 실험적 연구

김의환(Kim, Eui-hwan),강충식(Kang, Choong-shik),정철정(Jung, Chul-jung) 용인대학교 무도연구소 1992 武道硏究所誌 Vol.4 No.1