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.

Identification of a novel peptide that selectively binds to Kidney Injury Molecule-1 (KIM-1) by phage displayed peptide library

Tae-Jun Kwon,Joon-Suk Park,Sang-Hyun Kim,Enamul Haque,Byung-Heon Lee,Sang Eun Kim,Choong-Yong Kim,Sang Kyoon Kim 한국실험동물학회 2016 한국실험동물학회 학술발표대회 논문집 Vol.2016 No.2

알쯔하이머형 치매 환자에서 우울증의 유무에 따른 인지기능과 일상생활 수행능력의 차이

김승민,최태규,안석균,손석한,유계준,오병훈,오희철 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.2

연구목적 : 알쯔하이머형 치매 환자에게 있어서 중요한 행동증상중의 한가지인 우울증의 다양한 범위로 보고되고 있으며 우울증과 인지능력 및 기능적 능력과의 관계에 대한 연구가 매우 중요하게 부각되고 있다. 본 연구의 목적은 지역사회에 거주하는 경도 및 중등도의 알쯔하이머형 치매 환자를 대상으로 우울증이 일상생활 수행능력과 인지기능의 특정 영역과 연관이 있는지의 여부를 알아보기 위함이다. 방 법 : 본 연구대상은 경기도 광주군에 거주하는 65세 이상의 알쯔하이머형 치매 노인 48명이며, 한국판 Mini-Mental State Examination(이하 MMSE-K), 한국어판 신경행동학적 인지상태 검사(이하 한국어판 NCSE), 한국형 노인우울검사(이하 KGDS), 기본적인 일상생활 수행정도(이하 ADL), 그리고 도구적인 일상생활 수행정도(이하 IADL)를 연구도구로 하여 이들로부터 자료를 수집 조사하였다. 연구대상은 KGDS에 의해 우울 치매군과 비우울치매군으로 분류하였으며 두 군간의 상기 척도에 의해서 얻어진 결과를 χ²test 및 independent t-test를 이용하여 분석하였다. 결 과 : 우울 치매군과 비우울 치매군은 성별, 연령, 교육수준 및 MMSE-K 점수의 유의한 차이가 없었다. 우울 치매군은 비우울 치매군보다 ADL의 한 항목인 목욕하기에서 유의한 저하를 보였다. 우울 치매군은 비우울 치매군보다 IADL의 총점 및 식품점에 가서 장보기, 집안일(청소나 정리정돈), 금전 관리의 3개 항목에서 유의한 저하를 보였다. 그러나 우울 치매군은 비우울 치매군은 한국어판 NCSE를 이용한 인지기능의 영역별 비교에서는 유의한 차이를 보이지 않았다. 결 론 : 이상의 결과로 미루어 볼 때 알쯔하이머형 치매 환자에서의 우울증은 기본적인 일상생활 기능의 일부와 도구적인 일상생활 기능의 저하와 상당한 관련 있고, 이러한 우울증에 동반된 일상생활 기능의 저하는 인지기능의 영향에 기인하지 않는 것임을 시사된다. Objectives : Coexistence of depression is one of the important behavioral symptoms in patients with dementia of Alzheimer type. The study on the relationship between depression and cognitive abilities and /or functional abilities emerges as very important one. The aim of this study was to investigate whether depression is related to the impairment of daily activities and to certain areas of cognitive function in mild to moderate dementia of Alzheimer type. Methods : In this study, 48 patients with dementia of Alzheimer type among elderly community-residents in Kwangju, Kyunggi province, age 65 and older, were finally included. We examined their demographics and administered Korean Version of the Mini-Mental State Examination(MMSE-K). Korean Version of the Neurobehavioral Cognitive Status Examination (Korean version of NCSE), Korean Form of Geriatric Depression Scale(KGDS), Activities of Daily Living(ADL), and Instrumental Activities of Daily Living(IADL) to the subjects. We classified the subjects into two groups, dementia with and without depression on the basis of KGDS scores. The two groups were compared using χ²test and independent t-test. Results : The results show that the two groups did not differ in sex, age, education, and scores of MMSE-K. The depressed dementia group showed significantly poorer performance in bathing, one item of ADL, than the non-depressed dementia group. The depressed dementia group showed significantly more impairment in total scores of IADL and each score of three item(shopping, housework, handling finances) than the non-depressed dementia group. However, the two groups showed no significant difference in five major cognitive ability areas of Korean version of NCSE. Conclusion : These results suggest that depression in patients with dementia of Alzheimer type is highly related to the functional impairments, instrumental activities of daily living and part of activities of daily living, beyond the effects of cognitive impairments.

뇌하수체 종양 제거술 시행 후 뒤늦게 발생한 횡문근 융해증과 동반된 중추성 열

장제혁,최규남,김일환,노은지,김윤정,유충헌,고정해,박봉수,김태균,권민정,이순희,박정현 인제대학교 2008 仁濟醫學 Vol.29 No.-

Body temperature is controlled by thermoregulatory center of the hypothalamus. We report a case of 24 years old man with central fever. He was subjected to a partial excision of pituitary tumor compressing optic chiasm four years ago. He has received hormonal therapy for panhypothyroidism after removal of pituitary tumor. And He received gamma knife operation for partially contrast-enhancing masses in suprasellar and both hypothalamic areas that is probably postoperatively remnant or recurrent tumor of pituitary adenoma. One year after gamma knife operation, he presented with a febrile syndrome of unknown origin including rhabdomyolysis. All usual investigations proved negative. We diagnosed him as central fever with rhabdomyolysis. He received medical ICU care with cooling bed, ice pack. And his symptom improved. Postoperative hyperthermia may result following resection of the pituitary tumor. When central fever is suspected taking note of past history, a quick recognition of course of fever can help reduce the using of unnecessary antibiotics and hospital stay.

정신분열병 환자를 위한 인지재활훈련 프로그램의 개발 : Korean-Cognitive Differentiation Program 한국형 인지분화훈련 프로그램

현명호,안석균,이만홍,조현상,최충식,이연희,송선미,유계준,김장우,김태용,이희상 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.2

연구배경 : 정신분열병 환자들은 인지장애를 보이는바, 저자들은 이들을 대상으로 한국형 인지분화훈련 프로그램을 개발하여 정신분열병 환자들을 대상으로 인지재활훈련을 실시한 후 환자들의 인지기능, 정신병리 및 문제해결기술에 미치는 효과를 조사하였다. 방 법 : 28명의 정신분열병 환자를 훈련군(n=14)과 대조군(n=14)으로 나누어 훈련군에게 한국형 인지분화훈련 프로그램을 1회 60분씩, 주당 2회씩, 11주간 총 22회를 실시하였다. 환자들의 인지기능은 K-WAIS의 산수, 빠진곳찾기, 어휘, 공통점찾기 소검사로 측정하였고 정신병리는 양성 및 음성증상 척도로 측정하였으며 문제해결기술은 사회문제해결척도로 평가하였다. 인지재활훈련의 효과를 평가하기 위해 훈련 전후의 인지기능, 정신병리 및 문제해결기술의 변화를 종속변수로 하고 훈련 유무를 독립변수로 하여 반복측정에 의한 변량분석으로 자료를 분석하였다. 결 과 : 한국형 인지분화훈련이 시간에 따른 인지기능검사 중 산수 소검사, 문제해결기술 중 시회문제해결척도의 전체 점수와 문제해결기술 소척도의 점수의 변화에 유의한 영향을 미쳤으나, 시각적 주의력, 개념화 능력 및 정신병리의 점수의 변화에 유의한 영향을 미치지 않았다. 결 론 : 한국형 인지분화훈련 프로그램은 정신분열병 환자에서 청각적 주의력 및 문제해결기술의 호전을 꾀할 가능성이 있음을 시사한다. Objectives : The purpose of this study was to investigate the effects of cognitive differentiation training program- Korean version(a training program of attention and conceptual abilities) on cognitive function, psychopathology and problem solving skills in patients with schizophrenia. Methods : A total of patients diagnosed as schizophrenia using DSM-Ⅳ were randomly assigned to 2 groups. The training group went through a total of 22 sessions of cognitive differentiation training(60 min/ session×2 sessions/wk×11 wks). The attention-placebo control group received psychoeducation program during the same period. Arithmetic, vocabulary, similarities, picture completion of Wechsler Adult Intelligence Scale-Korean version, Positive and Negative Syndrome Scale, and Social Problem Solving Scales were administered to all patients, both before and after the training program. Results : In the arithmetic scores(F=6.35, af=1, p=0.018) of Wechsler Adult Intelligence Scale-Korean version, and total scores(F=6.35, af=1, p=0.018) and problem solving skill scale scores(F=4.88, af=1, p=0.036) of social problem solving scale, interaction effects of training was significant. Conclusion : Our findings suggest that cognitive differentiation training program-Korean version is effective on improving auditory attention and problem solving skills in patients with schizophrenia.

Nomogram for Predicting Breast Conservation after Neoadjuvant Chemotherapy

Kim, Min Kyoon,Han, Wonshik,Moon, Hyeong-Gon,Ahn, Soo Kyung,Kim, Jisun,Lee, Jun Woo,Kim, Ju-Yeon,Kim, Taeryung,Lee, Kyung-Hun,Kim, Tae-Yong,Han, Sae-Won,Im, Seock-Ah,Kim, Tae-You,Park, In Ae,Noh, Dong Korean Cancer Association 2015 Cancer Research and Treatment Vol.47 No.2

<P><B>Purpose</B></P><P>The ability to accurately predict the likelihood of achieving breast conservation surgery (BCS) after neoadjuvant chemotherapy (NCT) is important in deciding whether NCT or surgery should be the first-line treatment in patients with operable breast cancers.</P><P><B>Materials and Methods</B></P><P>We reviewed the data of 513 women, who had stage II or III breast cancer and received NCT and surgery from a single institution. The ability of various clinicopathologic factors to predict the achievement of BCS and tumor size reduction to ≤ 3 cm was assessed. Nomograms were built and validated in an independent cohort.</P><P><B>Results</B></P><P>BCS was performed in 50.1% of patients, with 42.2% of tumors reduced to ≤ 3 cm after NCT. A multivariate logistic regression analysis showed that smaller initial tumor size, longer distance between the lesion and the nipple, absence of suspicious calcifications on mammography, and a single tumor were associated with BCS rather than mastectomy (p < 0.05). Negative estrogen receptor, smaller initial tumor size, higher Ki-67 level, and absence of <I>in situ</I> component were associated with residual tumor size ≤ 3 cm (p < 0.05). Two nomograms were developed using these factors. The areas under the receiver operating characteristic curves for nomograms predicting BCS and residual tumor ≤ 3 cm were 0.800 and 0.777, respectively. The calibration plots showed good agreement between the predicted and actual probabilities.</P><P><B>Conclusion</B></P><P>We have established a model with novel factors that predicts BCS and residual tumor size after NCT. This model can help in making treatment decisions for patients who are candidates for NCT.</P>

Physicochemical Conjugation with Deoxycholic Acid and Dimethylsulfoxide for Heparin Oral Delivery

Kim, Sang Kyoon,Huh, June,Kim, Sang Yoon,Byun, Youngro,Lee, Dong Yun,Moon, Hyun Tae American Chemical Society 2011 Bioconjugate chemistry Vol.22 No.7

<P>Heparin, as therapeutic medications, cannot be administered orally because of its hydrophilic and high molecular weight. Here, we present a new technology to enhance the absorption of heparin in the intestine through its chemical conjugation with deoxycholic acid (DOCA) that can interact with bile acid transporter in the intestine. For the ampiphilic property and complete dissolution, the modified heparin was physically complexed with dimethylsulfoxide (DMSO). The DOCA-conjugated heparin could form nanoparticles in aqueous solution, whereas it was completely dissolved when treated with above 10% DMSO solution. Molecular dynamics computation study and two-dimensional homonulcear <SUP>1</SUP>H nuclear overhauser effect spectroscopy (NOESY) NMR spectra demonstrated that one heparin molecule was chemically conjugated with two DOCA molecules that were physically interacted with six DMSO molecules within 4 Å via hydrophobic interactions and partly via hydrogen bonding. Its therapeutic efficacy was also pharmaceutically analyzed. When the DMSO-bound DOCA-conjugated heparin was orally administered into mice, its therapeutic efficacy was enhanced according to the amount of bound DMSO. Also, after oral administration of fluorescence-labeled DMSO-bound DOCA-conjugated heparin, it was circulated in the whole body for above 2 h. However, the DOCA-conjugated heparin without DMSO binding was fast eliminated after oral absorption. This study demonstrates that the interaction of structural constraints, DOCA and DMSO, with heparin can serve as a platform technology for potential macromolecule oral delivery.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bcches/2010/bcches.2010.22.issue-7/bc100594v/production/images/medium/bc-2010-00594v_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bc100594v'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bc100594v'>ACS Electronic Supporting Info</A></P>

Non-viral EGF (Epidermal Growth Factor) gene therapy accelerated cutaneous wound healing in streptozotocin diabetic C57BL/6J mice (초)

( Tae Kyoon Kim ),( Min Jeong Kwon ),( Hye Sook Chung ),( Chang Shin Yoon ),( Soon Hee Lee ),( Mi Kyung Kim ),( Kyung Soo Ko ),( Byung Doo Lee ),( Jeong Hyun Park ) 대한내과학회 2008 대한내과학회지 Vol.75 No.1S

Non-viral EGF (Epidermal Growth Factor) gene therapy accelerated cutaneous wound healing in streptozotocin diabetic C57BL/6J mice (초)

( Tae Kyoon Kim ),( Min Jeong Kwon ),( Hye Sook Chung ),( Chang Shin Yoon ),( Soon Hee Lee ),( Mi Kyung Kim ),( Kyung Soo Ko ),( Byung Doo Lee ),( Jeong Hyun Park ) 대한내과학회 2008 대한내과학회 추계학술대회 Vol.2008 No.-

소장종양의 임상적 고찰

김해경,김병식,김진천,홍원선,남승우,민영일,정훈용,김해련,하현권,양석균,이재균,최재원,오성태 대한소화기학회 1998 대한소화기학회지 Vol.31 No.1

Background/Aims: Small bowel tumors are uncommon accounting for only 3 to 6% of all gastrointestinal tumors. The diagnosis of small bowel tumors has been usually made at an advanced stage because of the infrequency and absence of symptoms specific for early diagnosis, resulting in poor prognosis. This study was conducted to investigate the clinical features of small bowel tumors in Korea. Methods: We reviewed and analyzed clinical manifestations, laboratory results and survivals in 63 patients with small bowel tumors diagnosed at the Asan Medical Center between June 1989 and January 1996. Results: Among 63 tuors reviewed, 58 were malignant tumors and 5 were benign tumors. The malignant tumors consisted of 25 adenocarcinomas, 15 malignant lymphomas, 12 leiomyosarcomas and 6 metastatic carcinomas. Adenocarcinomas were located mainly in the duodenum and malignant lymphomas in the ileum or duodenum, while leiomyosarcomas were evenly distributed. Clinical symptoms of these patients included abdominal pain (71.4%), palpable mass (12.7%), weight loss (10.0%) and bleeding (8.0%). Anemia and positive stool occult blood test were found in 55.0% and 46.7%, respectively. The median duration of symptoms before the diagnosis was 4 weeks in malignant tumors and 36 weeks in benign tumors. Twenty-seven of 30 patients (90.0%) with duodenal tumors were diagnosed by duodenoscopy, while small bowel series and CT scans detected 9 of 11 (82.0%) and 25 of 35 (71.4%) small bowel tumors, respectively. The incidence of metastasis to regional lymph nodes and distant organs was higher in adenocarcinoma and malignant lymphoma than leiomyosarcoma. The 2-year survival rates for patients with adenocarcinomas, malignant lymphomas, and leiomyosarcomas were 23, 57, and 60%, respectively. Conclusions: These results suggest that small bowel tumors should be considered in patients having unexplained abdominal pain, anemia, and/or positive stool occult blood test.