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.

정상면역을 가진 성인에서 발생한 식도 방선균증

김현수 ( Hyun Soo Kim ),천종운 ( Jong Woon Cheon ),김민수 ( Min Su Kim ),정창길 ( Chang Kil Jung ),김경록 ( Kyung Rok Kim ),최재원 ( Jae Won Choi ),강동우 ( Dong Woo Kang ),김선영 ( Sun Young Kim ) 대한소화기학회 2013 대한소화기학회지 Vol.61 No.2

Hyun Soo Kim, Jong Woon Cheon, Min Su Kim, Chang Kil Jung, Kyung Rok Kim, Jae Won Choi, Dong Woo Kang and Sun Young Kim1 Departments of Internal Medicine and Pathology1, DongKang Medical Center, Ulsan, Korea Actinomycosis is a chronic suppurative disease and caused by Actinomycosis species, principally Actinomyces israelii, which are part of the normal inhabitant on the mucous membrane of the oropharynx, gastrointestinal tract, and urogenital tract. It usually affects cervicofacial, thoracic and abdominal tissue. Cervicofacial type has the highest percentage of occurrence with 50%. Actinomycosis frequently occurs following dental extraction, jaw surgery, chronic infection or poor oral hygiene. It may also be considered as an opportunistic infection in immunocompromised patients such as malignancy, human immunodeficiency virus infection, diabetes mellitus, steroid usage or alcoholism. But, actinomycosis rarely occurs in adults with normal immunity and rare in the esophagus. We report an unusual case of esophageal actinomycosis which was developed in a patient with normal immunity and improved by therapy with intravenous penicillin G followed oral amoxicillin, and we also reviewed the associated literature.

정상과 갑상선 종양조직에서 사람 IGF-I 유전자의 발현

김성운,장현하,박상미,김덕윤,우정택,양인명,김진우,김영설,김광원,고석환,홍성화,최영길 경희대학교 유전공학연구소 1993 遺傳工學論文集 Vol.5 No.-

Many of the growth-promoting properties of growth hormone(GH) are mediated by insulin-like growth factor-I(IGF-I), a highly conserved circulating 70-amino acid peptide. Recent studies have shown that multiple mechanisms influence IGF-I gene expression, including transcription from two promoters, alternative RNA splicing, and variable polyadenylation. In thyroid tissue, thyroid stimulating hormone(TSH) and IGF-I are the most possible candidates for follicular cell proliferation and hypertrophy. Actually IGF-I had autocrine and paracrine effect for tissue growing. We prepared thyroid tumor tissue mRNAs using single step method for detecting IGF-I levels according to different tissues, i.e., thyroid adenoma or papillary thyroid carcinoma. We used Northern blot analysis for IGF-I mRNA and RNase protection assay (RPA) for IGF-I transcription start sites. For Northern blot, we used whole human IGF-I cDNA as a DNA probe and for RPA, we used IGF-I exon 1 containing noncoding promoter 1 as a riboprobe. We got good RNA bands from Northern blot analysis around 1 kb (IGF-IA) and 7.5 kb (IGF-IB) region. To clarify the amount of both IGF-IA and IB mRNAs, we measured autoradiographied signal of IGF-I mRNAs bands using densitometer. In IGF-IA signals, there's no change among liver and thyroid tissues, but in case of IGF-IB mRNA bands, the signal was markedly increased in thyroid carcinoma tissues than that of normal thyroid tissue (85% vs 14%). In the study of RPA, all thyroid tissues used the same transcription start sites as those of liver's. We concluded that that this different regulation of IGF-I mRNA was originated from tissue specificity. That meant some tissue specific transcription factor/s were related to tissue IGF-I expression.

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.

골아세포 MC₃T₃-E₁의 증식과 기능에 Insulin Like Growth Factor Ⅰ, Ⅱ 및 부갑상선 호르몬이 미치는 영향

윤현구,정호연,양인명,김성운,김진우,김광원,김영설,최영길,서광식 대한내과학회 1992 대한내과학회지 Vol.42 No.1

MC₃T₃-E₁골아세포군을 이용하여 IGF-Ⅰ과 Ⅱ를 투여하고 DNA합성과 골아세포기능을 측정하기 위해 PTH에 대한 C-AMP반응정도, alkaline phosphatase 활성도를 측정하여 다음과 같은 결과를 얻었다. 1) IGF-Ⅰ과 Ⅱ는 모두 DNA합성이 어느 농도까지는 증식효과를 나타내지만 그 이후에는 억제되는 양상을 보였다. 2) PTH에 대한 골아세포의 C-AMP반응으로 증가되었지만 IGF-Ⅰ과 Ⅱ의 투여시 농도변화에 따른 의미있는 변화는 없었다. 3) 본 실험의 조건에서 alkaline phosphatase 활성도는 증가되지 않았다. 이상의 결과로 MC₃T₃-E₁ 골아세포에 IGF-Ⅰ과 Ⅱ는 세포의 증식을 자극하여 PTH는 C-AMP생성을 촉진하는 효과가 있었다. The effect of insulin-like growth factor (IGF) Ⅰ and Ⅱ on cloned MC₃T₃-E₁ cells that had osteoblastic activity was examined by [³H] thymidine incorporation into DNA, cyclic AMP responsiveness to parathyroid hormone (PTH), and alkaline phosphatase activity. IGF Ⅰ and Ⅱ stimulated the growth and proliferation of osteoblastic cells at 20ng/㎖ and 50ng/㎖, respectively. We next examined the effect of IGF-Ⅰ and Ⅱ on the expression of osteoblastic activity. Adenylate cyclase response of PTH to IGF-Ⅰ and Ⅱ-treated cells showed maximal stimulation at 10 and 50㎚PTH, respectively, but IGF Ⅰ and Ⅱ induced limited activity of osteoblastic function. In conclusion, IGF-Ⅰ and Ⅱ were potent stimulators to the growth of osteoblastic cells but did not have an immediate effect on expression of osteoblastic function in this experiment.

제초제(propanil. butachlor) 저항성 잡초 선발 방법에 관한 연구

정성엽,김영미,박재현,이재현,김학윤,이인중,신동현,김길웅 경북대학교 농업과학기술연구소 1999 慶北大農學誌 Vol.17 No.-

This study was conducted to develop a simple selection method for herbicide-resistance weeds. Two methods, designated "seedling method" and "stem node method" were employed for screening of barnyardgrass against propanil and butachlor. In the seedling method, shoot and root growth of barnyardgrass were significantly inhibited at quarter of the recommended herbicide rate, while in the stem node method, the similar inhibition was obtained at half of the recommended rate. Thus, it was concluded that the seedling method is more simple and quick method to evaluate response of barnyardgrass to propanil and butachlor compared to stem node method.

생체분해성 고분자를 이용한 사시수술용 제형개발 및 효용성에 대한 연구

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

A new device, muscle clamping system was developed to facilitate exact quatifying technique A strabismus surgery, and reduce the risk of complications. The device is composed of a lower fixing body with three jaws and an upper supporting body. They are used to clip an extraocular muscle and fix it to the sclera with a single bite. Superior rectus recession on 16 rabbit eyes were performed with this new device. Conjunctival injection, muscle adhesion strength, and light microscopic findings were examined at 1, 2, 4 and 8 weeks postoperatively. The Conjunctival injection were minimal, adhesion power ranged from 420 to 600 gram gravity, which is sufficient in withstand the normal pull of human extraocular muscle. In microscopic exam, some Inflammatory cells and fibrosis were found. The new device was technically easy, fast, and accurate, so it may be useful in stabismus surgery.

비만증 환자에서 한약제에 의한 체중 감소효과

Oh, Seung-Joon,Jeong, In-Kyung,Kim, Young-Seol,Choi, Young-Kil,Paeng, Jeong-Ryung,Bae, Jung-Hwan,Shin, Hyun-Dae 경희대학교 동서의학연구소 1999 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.1999 No.1

Seung-Joon Oh, In-Kyung Jeong, Young-Seol Kim, Young-Kil Choi, Jeong-Ryung Paeng¹, Jung-Hwan Bae and Hyun-Dae Shin²Department of internal Medicine, College Medicine, Endocrine Research Institute¹. Department of Rehabilitation, College of Oriental Medicine², Seoul, korea. Bady Fat Reduction Effects of Red Ginseng Compound Preparation on the Patients with Obesity. Proceedings of International Symposium on East-West Medicine, Seoul. 244-254, 1999.-Obesity can be defined as a metabolic disease due to an increased state of fat tissues caused by an imbalance of calorie intake and use. Recently, in Korea by improvement and westernization of food intake, along with decrease in exercise activities, the prevalence of obesity has increased greatly. Our objectives were to study stability and effects of decrease in body fat by administering red ginseng compound preparation (known to have body fat decreasing effects in laboratory animals) to obesity patients on low calorie diets. Changes in weight and body fat were measured while carrying out calorie-restricted diets on patients for 4 weeks, then administering red ginseng compound preparation for another 4 weeks. The patients were 20 people whose BMI were 25kg/㎡ or over and whose percent body fat was also 30% or over when tested by bioelectrical conductivity. 1. Changes in weight were from 70.04kg(base line) to 67.43kg(after taking red ginseng compound preparation). 2. In similar sense, BMI decreased from 27.12kg/㎡(base line) to 26.56kg/㎡(after dieting), and further to 26.01kg/㎡ (after taking red ginseng compound preparation). The BMI seemed to decrease significantly compared to the baseline after the use of red ginseng compound. 3. Waist hip ratio was changed from 0.8858(base line) to 0.8728, but it was statistically insignificant. 4. The percent body fat was 35,16%(base line), 33.87%(after dieting), and 31.68%(after taking red ginseng compound preparation). 5. Complete blood cell count and blood chemisrty remained unaffected by the administration. 6. In concern to endocrinologic studies, T3 decreased from 118.7 to 98.2ng/dL, and T4 increased from 8.8 to 9.2㎕/ dL. Epinephrine showed a tendency to decreased from 0.27 to 0.25 ng/mL, and norepinephrine increased from 0.39 to 0.44ng/mL. 7. Leptin was not changed. 8. Some patients complained adverse effects; constipation(5 patients, may be due to diet therapy), fatigue (2 patients), pruritus(2 patients), flushing(s patients), dizziness(3 patients) and epigastric discomfort(2 patients). However their symptoms were mild, so medication did not stopped. In conclusion, loss of weight without significant side effects was observed during low calorie diet and red ginseng compound preparation administration. This is thought to be in relation to sympathetic nerve system rather than adrenal gland. Also, further long0term studies should be required, since the observed results were based on short-term changes in weight.

당뇨병 환자에서 혈장 Thrombin-Antithrombin Ⅲ 및 Plasmin-α_2-Plasmin Inhibitor 복합체의 임상적 의의

김경욱,김은숙,정상수,윤수지,박우일,이준희,남수연,안철우,문병수,김경래,차봉수,송영득,임승길,이현철,허갑범 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.5

연구배경:당뇨병 환자에서 혈액응고 및 섬유소용해 체계의 이상경향이 있어 그 결과로 여러 혈관합병증의 발생위험이 높다는 사실은 널리 알려져 있다. 그 기전은 아직 확실히 밝혀지지 않았으나, 고혈당으로 인한 혈장 단백질들의 비효소성 당화작용이나 산화성 스트레스로 인한 유리 라티칼 작용으로 응고항진이나 섬유소용해 활성의 저하를 유발하는 것으로 생각되고 있다. 최근 응고 및 용해인자와 그 억제자의 복합체들의 증가가 이 상태를 비교적 예민하게 반영한다고 알려져 있다. 방법:본 연구에서는 당뇨병 환자 101명과 정상 대조군 20명에서 혈장내 thrombin­antithrombin complex(TAT)와 plasmin­α₂­plasmin inhibitor complex(PIC)를 측정하여 비교하고, 당뇨병 환자에서 미세혈관 합병증과 대혈관합병증의 유무에 따른 차이와, 이미 혈관 질환의 위험인자로 알려져 있는 인자들간의 상관성을 알아보고자 하였다. 결과:1. 환자의 분포를 살펴보면 혈관합병증이 있는 군은 85명, 혈관합병증이 없는 군은 16명이었고, 평균연령은 각각 57.9±14.1세, 49.9±16.6세로 혈관 합병증이 있는 군에서 더 나이가 많았고, 체질량지수는 23.2±3.4㎏/㎡, 24.1±3.4㎏/㎡로 두 군간 유의한 차이는 없었다. 또 두 군간의 혈압 및 HbA1c, 공복혈당 및 인슐린과 C­peptide, 총 콜레스테롤, 중성지방, HDL­콜레스테롤, Lp⒜는 유의한 차이가 없었고, 미세혈관합병증이 있는 군에서 당뇨병의 유병기간이 길었다. 2. TAT 및 PIC의 농도는 정상 대조군에서는 2.8±1.2 ng/mL, 240.4±69.7 ng/mL이었고, 당뇨병 환자군에서는 9.5±22.6 ng/mL, 472.2±258.7 ng/mL이었다. TAT와 PIC 모두 당뇨병 환자군에서 정상 대조군에 비해 유의하게 증가되어 있었고(p<0.001), TAT/PIC ratio는 두 군간 차이가 없었다. 3. 당뇨병 환자의 혈관합병증에 따른 TAT 및 PIC, fibrinogen 농도는 합병증이 없는 군은 각각 4.1±2.4ng/mL, 362.2±272.0ng/mL, 322.7±102.4mg/mL으로 PIC와 fibrinogen의 증가를 보였으나, 연령을 보정한 후에는 통계학적 유의성은 없었다. 또 대혈관 합병증군에서는 각각 6.0±4.9 ng/mL, 507.4±321.6 ng/mL, 427.1±194.7 mg/dL이었으며 미세·대혈관 합병증군에서는 10.4±6.4 ng/mL, 484.8±269.7 ng/mL, 388.4±132.4 mg/dL으로 TAT의 증가를 보였으나 역시 연령을 보정한 후에는 통계학적 유의성은 없었다. 4. 미세혈관합병증군에서 HbA1c(>8%)가 높은 군의 PIC 농도가 유의하게 높았고(p=0.049), 대혈관합병증군에서 HbA1c(>8%)가 높은 군의 총 콜레스테롤 농도가 유의하게 높았다(p=0.042). 5. 총 당뇨병 환자군에서 PIC는 fibrinogen과 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며(r=0.47, 0.31,-0.25), 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다(r=0.67). 결론:이상의 결과에서 혈장 TAT 및 PIC 농도는 당뇨병 환자에서 정상 대조군에 비해 의미있게 증가되어 있었고, 당뇨병 환자군에서는 연령의 증가와 유병기간이 혈액응고항진 및 용해의 장애에 큰 역할을 함을 알 수 있었으며, 총 당뇨병 환자군에 PIC와 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다. 따라서 당뇨병 환자에서 혈액응고 및 용해의 장애가 동반되어 있다고 볼 수 있으며, 혈장 TAT 및 PIC는 혈관합병증으로의 진행을 예측하는 지표로서 유용하리라 생각된다. 또 혈당조절정도와 상관성이 있으므로 혈당조절후에 추적검사를 시행하여 합병증의 예방이 가능한지 추후 연구가 필요하리라 생각된다. Background : Abnormality of coagulation and fibrinolystic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin Ⅲ complex (TAT) and plasmin-α_2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. Methods : In our study, we measured plasma thrombin-antithrombin Ⅲ compelx (TAT) and plasmin-α_2-plasmin inhibit or complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. Results : 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA_ic, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8±1.2 ng/ mL, 240.4±69.7 ng/ mL in controls and 9.5±22.6 ng/ mL, 472.2±258.7 ng/ mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1±2.4 ng/ mL, 362.2±272.0 ng/ mL, 322.7±102.4 mg/ dL in group without vascular complication and 5.3±4.1 ng/ mL, 529.5±258.7 ng/ mL, 374.9±106.2 mg/ dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 60.±4.9 ng/ mL, 507.4±321.6 ng/ mL, 427.1±194.7 mg/ dL in macrovascular complication, and 10.4±6.7 mg/ mL, 484.8±269.7 ng/ mL, 388.4±132.4 mg/ dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA_1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA_1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA_1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA_1c (r=0.67). Conclusion : In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA_1c. TAT was correlated with HbA_1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients (J Kor Diaabetes Asso 25:354~363, 2001).

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김진모,주대진,이진화,길대환,주현미,이정은 한국농업교육학회 2007 농업교육과 인적자원개발 Vol.39 No.2