Development of a noninvasive KIM-1-based live-imaging technique in the context of a drug-induced kidney-injury mouse model

Tae-Jun Kwon,Da-Sol Lee,Md. Enamul Haque,Rang-Woon Park,Byungheon Lee,Dongkyu Kim,Yong-Hyun Jeon,Kil-Soo Kim,Sang Kyoon Kim 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

The development of reliable methods to diagnose acute kidney injury is essential to allow the adoption of early therapeutic interventions and evaluate their effectiveness. Based on the fact that kidney injury molecule-1 (KIM-1) expression levels in kidneys are markedly upregulated early after a damage event, here we developed a noninvasive KIM- 1-based molecular imaging technique to detect kidney injury. First, we took advantage of a phage-display platform to select small peptides demonstrating a specific high binding affinity to KIM-1. The promising candidate was conjugated with fluorescent probes, and its imaging potential was validated in vitro and in vivo. This peptide, with the sequence CNRRRA, not only showed a high imaging potential in vitro, allowing a strong detection of KIM-1 expressing cells by microscopy and flow cytometry but also generated a strong kidney-specific signal in live-imaging in vivo experiments in the context of a drug-induced kidney-injury mouse model. Our data overall suggest that the CNRRRA peptide is a promising probe to use in the context of in vivo imaging for the detection of KIM-1 overexpression in damaged kidneys.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

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.

운동이 백서 스테로이드 근병증에 미치는 효과

박상준,이민철,김세종,박상준,이민철,김세종 대한신경과학회 1999 대한신경과학회지 Vol.17 No.5

메티실린 내성 황색 포도상구균에서 vancomycin과 gentamicin병용의 항균력 상승효과 : Gentamicin 감수성에 따른 영향

김양수,김은옥,이상오,김백남,류지소,배직현,우준희,김미나,정두련,박수진 대한감염학회 1998 감염 Vol.30 No.2

배 경 : Vancomycin은 메티실린 내성 황색 포도상구균(methicillin-resistant Staphylococcus aureus, MRSA) 감염치료 시 선택 약제이다. 그러나, MRSA에 의한 심내막염과 같은 심부감염에서는 vancomycin 단독치료로 실패하는 경우가 흔히 보고되고 있다. MRSA에서 vancomycin과 aminoglycoside 병용의 상승효과에 대하여는 기존의 연구가 많지 않았다. 따라서 본 연구에서는 MRSA에서 vancomycin과 gentamicin 병합 시 상승효과가존재하는지를 알아보고, 만일 상승효과가 있다면 이를 예측할 수 있는 gentamicin의 최소억제농도를 밝히고자 하였다. 방 법 : 임상검체로부터 분리된 MRSA균주 중 무작위로 51균주를 선택하여 한천 희석법으로 gentamicin에 대한 최소 억제농도를 측정하였다. 이들 중 다양한 최소억제농도를 가지는 25균주에 대하여 vancomicin에 대한 최소억제농도와 최소살균농도를 측정하여 vancomycin에 대한 내약성(tolerance)여부를 조사하였고, vancomicin과 gentamicin 단독 및 병합에 대한 "time-kill 연구"를 시행하였다. 결 과 : MRSA 51균주에 대한 gentamicin의 최소억제농도는 4μg/mL 이하에서 512μg/mL 이상의 범위였으며, 7균주(13.7%)에서 감수성을 보였고 나머지 44균주(86.3%)는 내성이었다. 선택된 25균주의 MRSA 모두가 vancomycin에 감수성을 보였으나 16균주(64.0%)는 vancomycin에 tolerance를 보였다. Time kill 측정에서 약물 상호 작용의 분석이 가능하였던 18균주 중 5균주(27.8%)에서 상승효과가 관찰되었으며 나머지 13균주(72.2%)는 상호 무관한 작용을 보였다. 상승효과를 보인 5균주 모두가 gentamicin 최소억제농도 32μg/mL 이하이었으며, gentamicin 최소억제농도가 64μg/mL 이상인 균주 중 상승 작용을 보인 균주는 없었다. 결 론 : 메티실린 내성 황색 포도상구균의 대부분은 gentamicin에 내성을 보이지만, gentamicin에 내성이 있는 경우라도 gentamicin 최소억제농도가 32μg/mL 이하라면 vancomicin과 gentamicin을 병합 치료하여 상승효과를 기대할 수 있을 것으로 생각된다. Background : Vancomycin is the drug of choice for the treatment of infections caused by methicillin-resistant Staphylococcus aureus(MRSA). However, vancomycin monotherapy of deep-seated staphylococcal infection may be associated with poor bacteriological response. Limited data suggest that vancomycin-gentamicin combination therapy is effective against MRSA. In this study, we evaluated the vancomycin-gentamicin synergism against MRSA and also investigated whether gentamicin susceptibility may affect the synergism. Materials and Methods : The 51 strains of MRSA were obtained from patients at the Asan Medical Center from 1995 to 1996. The minimal inhibitory concentrations(MICs) of gentamicin were determined by the agar dilution method. The 25 strains with various levels of gentamicin MICs were chosen for time-kill studies. The MICs and minimal bactericidal concentrations(MBCs) of vancomycin were defined to determine vancomycin tolerance. Time-kill curves were established with vancomycin, gentamicin, and a combination of both. Results : Gentamicin MICs ranged from 4 to 512 μg/mL. Only 7 of the 51 strains were gentamicin-susceptible and 44 were resistant. All of the 25 strains chosen were susceptible to vancomycin, but 16 of them showed tolerance. Vancomycin-gentamicin synergism was demonstrated in 5 of the 18 strains, in which the analysis of drug interaction was possible. In the remaining 13 strains, vancomycin and gentamicin interacted in a nonsynergistic manner. In all strains that showed synergism, the MICs of gentamicin were below 32 μg/mL. No synergism was demonstrated in strains with gentamicin MICs above 64 μg/mL. Conclusions : Although most of MRSA strains are resistant to gentamicin, synergistic interaction between vancomycin and gentamicin may be expected when the MIC of gentamicin is below 32 μg/mL.

The effect of neuropeptides on secretion of Interleukin-8(IL-8)

Kim, Kyung-Jun,Park, Sang-Hyuk,Choi, Kyoung-Kyu,Park, Sang-Jin 大韓齒科保存學會 2006 Restorative Dentistry & Endodontics Vol.31 No.3

본 연구는 치수조직, 치은, 치주인대로부터 배양된 조직을 SP (Substance P)로 4시간, SP, CGRP (Calcitonin Gene-related Peptide), Tumor necrosis factor-α (TNF-α)로 8시간 자극 후 RNase Protection Assay를 시행하고, IL-8의 분비량을 측정해 다음 결과를 얻었다. 1. IL-8 mRNA는 모든세포에서 발현됐다. 2. IL-8 mRNA 발현은 SP (10^(-5)M)와 SP (10^(-8)M)로 4시간 자극 시 증가되지 않았다. 3. IL-8 mRNA 발현은 SP (10^(-4)M)와 CGRP (10^(-6)M)로 8시간 자극 시 증가되지 않았다. 4. TNF-α (2 ng/㎖) 자극 시, IL-8 mRNA 발현이 증가됐다. 5. 치은 세포를 CGRP (10^(-6)M)로 8시간 자극 시, IL-8 분비량이 증가했다 (p < 0.05). 6. 치주인대 세포를 SP (10^(-4)M)로 8시간 자극 시 IL-8 분비량이 증가했다 (p < 0.05). We investigated the secretion of Interleukin-8 (IL-8) from ginviva and periodontal ligament stimulated with Substance P (SP) and Calcitonin Gene-related Peptide (CGRP). Gingiva (GF), periodontal ligament (PDLF) and pulp (PF) tissues were collected from extracted instact 3rd molars. Cultured cells were stimulated with different concentrations of SP for 4 hrs, and stimulated with SP, CGRP and Tumor Necrosis Factor-α (TNF-α) for 8 hrs. Then RNase Protection Assay was carried out. ELISA was performed using supernatants of stimulated cells for quantitative analysis of IL-8. Results were assessed using supernatants of stimulated cells for quantitative analysis of IL-8. Results were assessed using student t-test with significance of P < 0.05. According to this study, the results were as follows: 1. IL-8 mRNA was detected in all type of cells studied (PF, GF and PDLF). 2. IL-8 mRNA expression was not increased after stimulating 4 hrs with SP (10^(-5)M) and SP (10^(-8)M) compared with Mock stimulation in all type of cells studied. 3. IL-8 mRNA expression was not increased after stimulating 8 hrs with SP (10^(-4)M) and CGRP (10^(-6)M) compared with Mock stimulation in all type of cells studied. 4. TNF-α (2 ng/㎖) increased the expression of IL-8 mRNA in all kind of cells studied. 5. The secretion of IL-8 from GF was increased 8 hrs after the stimulation with CGRP (10^(-6)M) (p < 0.05). 6. The secretion of IL-8 from PDLF was increased 8 hrs after the stimulation with SP (10^(-4)M) (p < 0.05). Calcitonin Gene-related Peptide (CGRP) increased Interleukin-8 (IL-8) which plays an important role in chemotaxis of neutrophil in Calcitonin Gene-related Peptide (CGRP) gingival tissue, whereas Substance P increased the secretion of IL-8 from periodontal ligament.

생체분해성 망막압정을 이용한 망막고정에 대한 실험적 연구

김용백,민병무,김창식,박근성,김승영,길숙종,조항진,이성복,노승무,송규상,강대영,조준식,양준묵,정경수,최선웅,이진호,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

Biodegradable retinal fixation devices obtain mechnical fixation of the retina with desirable chorioretinal scarring and with the potential for local, sustained release of antimetabolites and steroids to inhibit proliferative vitreoretinopathy. We manufactured a biodegradable retinal tack with barb that was designed in order to prevent intrusion from implantation of retinal tacks. This study was carried to evaluate the efficacy for retinal fixation and the capability for sustained release of drugs with a newly designed biodegradable retinal tack Biodegradable retinal tacks were made of polymers of glycolic acids and were designed with barbs in a shape to prevent the disinsertion. Biodegradale retinal tacks are divided into 3 parts, a conical portion that is inserted into the sclera, a cylinder portion that remains in the vitreous, and a neck portion between the pin and the cylinder. The tapered conical end was manufactured to allow easy insertion through the retina and choroid into the sclera. A cylinder portion was manufactured with a tapered angle that fixes firmly into the orifice of 19 gauge spinal needle. A neck portion, 0.4 mm in diameter, was designed to prevent disinsertion from following implantation of retinal tack. The applicator was a 19 gauge spinal needle and its orifice was prepared to 15°angle to accept the tapered cylinder portion of the retinal tack. The retinal tacks, secured in the needles, were passed through the formed vitreous and inserted into the retina, choroid, and sclera and were released by pushing the internal needle, usually within 2-3mm of the medullary ray of the posterior rabbit retina A retinal tack was placed in each of 8 pigmented rabbit eyes. Slit-lamp biomicroscopy, indirect ophthalmoscopy and fundus photography were performed periodically from 1 day to 8 weeks after surgery. Eight eyes were enucleated and studied by light microscopy at 8 weeks. Biomicroscopic evaluation of the animals revealed edemas adjacent to the retinal surfaces immediately after insertion of the biodegradable retinal tacks in all the animals. These edemas disappeared after 1 week. The first noticeable change in the size of retinal tacks was shown after 2weeks. The size of the retinal tacks gradually got smaller, decreasing to about one-half at 4 weeks and about one-third at 8 weeks. All retinal tacks remained in inserted places without any movement for an 8 week period. On light microscopy, epiretinal proliferations were seen to extend into the vitreous cavity. Cellular capsules that lined the inner aspect of the scleral defect caused by tack insertion were found. However the adjacent retina had a normal cytologic appearance and architecture in all specimens. We manufactured a biodegradable retinal tack that is designed to prevent intrusion from implantation of retinal tacks. All biodegradable retinal tacks reduce in size with time, but no retinal tacks extruded from the inserted place. The newly designed biodegradable retinal tack can be used for retinal fixation and may be used as a vehicle for the introduction of pharmacologic agents to prevent the cellular events that promote proliferative vitreoretinopathy.

서울의 PPNG 발생 빈도(1991-1992)

김재홍,윤기범,박평원,김영진,전경민,김영태,김중환,곽호,구상완,송민석,유옥,지혜구,김동원,문상은,박영립,정승호,성범진,성순제,엄주용,황정열,이기홍,이주협,전태진 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.1

The prevalence of PPNG among pretreated gonorrhea cases isolated at the STD clinic of Choong-Ku Public Health Center in Seoul has been studied and reported annually since 1981. In 1991, 123 strains of N.gonorrhoeae were isolated, among which 58(47.1%) were PPNG. In 1992, 98 starains of N.gonorrhoeae were isolated, among which 51(52.0%) were PPNG. In all, 109(49.3%) strains were found to be PPNG among 221 strains isolated between 1991-1992. The prevalence of PPNG in Seoul showed increased tendency till 1989, thereafter, it has been stationary or slightly decreasing.

간이식 환자에서 발생한 Aspergillus fumigatus에 의한 고관절염 1예

김탁,이상록,조오현,박기호,오련,이상오,김양수,우준희,김미나,최상호 대한감염학회 2008 감염과 화학요법 Vol.40 No.3

저자들은 간이식을 받은 환자에서 조직 배양 검사를 통하여 진단된 A. fumigatus에 의한 화농성 고관절염을 경험하였기에, 문헌 고찰과 함께 보고하는 바이다. Septic arthritis is an uncommon finding of invasive Aspergillosis. It can be caused by direct inoculation, Post-surgical infection, and hematogenous spread. Articular aspergillosis often involves the knee. A 49-year-o1d man who received a liver transplant in China on two months ago, due to liver cirrhosis caused by hepatitis B virus was admitted because of left side hip pain. Hip MRI showed joint effusion and bony destruction of the left hip and acetabulum. Incision and drainage was done and Aspergillus fumigatus was isolated from the resected tissue. After eight weeks of amphotericin B therapy, total hip replacement arthroplasty was done. Oral itraconazole 400mg/day was prescribed for six months after operation. The patient is now doing well without physical restriction.