Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

Won, A Jin,Kim, Siwon,Kim, Yoon Gyoon,Kim, Kyu-Bong,Choi, Wahn Soo,Kacew, Sam,Kim, Kyeong Seok,Jung, Jee H.,Lee, Byung Mu,Kim, Suhkmann,Kim, Hyung Sik The Royal Society of Chemistry 2016 Molecular bioSystems Vol.12 No.1

<P>The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg(-1), i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-alpha (GST-alpha), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.</P>

레트로바이러스벡터를 이용한 제대혈 세포에 유전자이입시 염화칼슘 농도와 싸이토카인의 효과

김성배,김상희,이정신,최성준,김정균,이제환,김상위,서철원,이규형,김우건 대한조혈모세포이식학회 1998 대한조혈모세포이식학회지 Vol.3 No.1

연구배경 : 혈액 세포에 레트로 바이러스를 이용한 유전자 이입시 이입 효율성이 낮은 것이 중요한 장애 요인이 된다. 이를 극복하기 polycation을 첨가해 왔다. 제대혈 단핵세포가 유전자 이입 표적세포로써 적절한지를 알아보고, polycation 첨가방법과 비교하여 유전자 이입시 레트로 바이러스 상층액에 싸이토카인과 염화 칼슘 농도가 유전자 이입에 미치는 영향을 살펴 보고자 하였다. 방법 : 레트로 바이러스 상층액에 일정량의 3가지 싸이토카인(IL-3, IL-6,SCF)과 4가지 종류의 염화 칼슘 농도를 달리하여 첨가한 후 제대혈 단핵세포에 유전자 이입을 하였다. 유전자 이입시킨 제대혈 단핵세포(2×106)를 4개씩 plating 한 후 이중 2개의 well에는 G418(1.0㎎/ml)를 첨가하여 G418 처리한 배지에서 형성된 집락수를 세었다. 동일한 실험을 3회 반복하였다. 결과 : 1) 싸이토카인을 사용하였을때 , IL-3 단독 사용시 보다는 IL-3, IL-6, SCF 혼합 사용시 유전자 이입 효율성이 4.1 배 6.8배 각각 증가되었다. 2) 간질 세포 존재 유무는 유전자 이입 효율성에 직접적인 영향을 주지는 않았다. 3)싸이토카인 첨가유무, 간질세포 조건에 상관없이 염화 칼슘 농도가 증가함에 따라 유전자 주입률이 3.6배 향상되었다. 4) 기존의 polybrene만 처리하였을때 보다 염화칼슘 농도를 올림으로써 유전자 이입에 사용되지 않고 버리는 레트로바이러스가 74%에서 29%로 감소 하였다. 5) 염화칼슘농도가 5mM 초과시에는 methylcellulose 배지에서 colony 수가 감소되었다. 6) G418 처리후 살아남은 colony는 PCR을 통해 Neo® 이 이입되었기 때문임을 확인할 수 있었다. 결론 : 싸이토카인 및 염화칼슘을 처리하여 유전자 이입 효율을 향상시킬수 있었고 생체 외에서 이러한 염화칼슘 침전법을 이용한 유전자 이입은 바닥에 붙어 자라는 세포(anchorage-dependent cell)를 대상으로 할때 더욱 효과적일 것으로 생각하며, 성공적인 유전자 치료에 필수적인 유전자 이입 효율성을 향상시키기 위해 더 많은 연구가 뒷받침 되어야 겠다. Background : Low transduction efficiency has the main obstacle for retroviral mediated gene transfer into hematopoietic cells even with the addition of polycations to enhace transduction. We investigested the feasibility of mononuclear of CaCl₂ added to retroviral supernatant compared to the standard polybrene-enhanced transfection. Methods : Cell free Neo^(R) retroviral supernatant containing 3 cytokines (Ⅱ-3, IL-6, SCF) with 4 different concentrations of CaCl₂ was added to target cells. After gene transfer, the cells(2×10^(6)/ml) were plated in qudriplicate, G418 was added to 2 wells of each set at 1.0 ㎎/ml, measured the percentage of G418 resistant progenitor derived colonies. Results : 1) Use of cytokines or especially combined use of 3 cytokines (IL-3, IL-6, SCF) together increased gene transfer efficiency to 6.8 times as compared to transductions in basal medium. 2) The presence of stromal supports during the transduction of the umbilical cord mononuclear cells did not increase gene transfection efficiency. 3) Transfection efficiency of CBMNCs (cord blood mononuclear cells) could be enhanced to 3.5 times by increment of CaCl₂. 4) Discarded retrovirus with standard polybrene-enhanced method could be reduced from 74% to 29% as the increase of CaCl₂ of the retroviral supernatant. 5) The number of colonies in methycellulose culture constantly reduced above 5mM CaCl₂. 6) Neo^(R) gene transfection in selected colony with G418 was confirmed by DNA-PCR. Conclusion: We conclude that tranduction to umbilical cord blood progenitor cells could be enhanced to 6.8 or 3.6 times with the use of recombinant human growth factors(IL-3, IL-6, SCF) and the increment of CaCl₂ concentration added to retroviral supernatant, but it might be ctyotoxic above 5 mM. Where the use of the calcium coprecipitation method is contemplated in ex vivo gene therapy, anchorage-dependent target cells are more desirable.

Cochlodinium polykrikoides 의 성장에 미치는 물리 , 화학적 요인과 영양염 이용

김형철(Hyung Chul Kim),이창규(Chang Kyu Lee),이삼근(Sam Geun Lee),김학균(Hak Gyoon Kim),박청길(Chung Kil Park) 한국수산과학회 2001 한국수산과학회지 Vol.34 No.5

우리나라 남해안에서 매년 유해 편모조류인 Cochlodinium polykrikoides 적조가 발생하고 있으며 많은 수산피해를 일으키고 있다. 본 연구는 본 종에 대한 적조발생기구를 구명하는데 있어 생물학적인 기초를 확립하기 위해 실시되었다. 실험실 배양실험을 통해 물리·화학적 환경요인에 대한 C. polykrikoides의 성장을 조사하였고, 그 결과를 요약하면 다음과 같다. 해양에서 발생하는 C. polykrikoides 자연군집의 동역학중에서 물리·화학적 환경요인의 상대적인 중요성을 평가하기 위해 수온, 염분, pH, 조도 조건별로 무균배양을 통한 본 종의 성장을 조사 하였다. 그 결과는 25℃, 40‰, pH 7.5, 7,500 lux에서 가장 성장률이 높았다. 그리고, 19∼28℃에서도 성장이 잘 이루어져 광온성(eurythermal) 종으로 확인되었으며, 발생해역의 염분 범위인 30∼35‰ 환경조건을 만족하는, 즉 내만의 저염분보다는 외양의 고염분 환경에서 발생하여 성장하는 종으로 확인되었고, 광염성(euryhaline) 종이다. 그리고, 높은 일사량을 요구하며 현장해역의 pH 범위에서 성장이 원활히 이루어졌다. 무기태 영양염인 질소원으로 질산질소와 암모니아질소를, 인원으로 인산인을 이용하여 C. polykrikoides의 영양염에 대한 성장 실험을 하였다. 그 결과, C. polykrikodes의 영양요구량은 질산질소, 암모니아질소, 인산인에 대해 각각 40, 50, 5㎛이었고, 성장에 의한 반포화상수 (Ks)값은 각각 2.10, 1.03, 0.57㎛로 확인되었다. 이러한 결과로부터 C. polykrikoides는 타와편모조류에서 보고된 Ks 값보다 대체적으로 낮았고, 빈영양성 (oligotrophic) 종은 아니며, 부영양성 (eutrophic) 종에 해당하지만 암모니아질소 Ks 값은 부영양성 종보다 낮은 값을 가지는 것으로 나타났다. 이것은 C.polykrikoides 적조는 내만의 부영양화된 해역보다는 부영양상태가 높아지고 있는 해역에서 발생할 가능성이 매우 높은 것을 나타낸다. 또한, C. polykrikoides는 질산질소보다 암모니아질소를 성장시 보다 유효한 영양염으로 선택하여 소비하였다. 이것은 암모니아질소가 타 영양염보다 성장에 보다 중요한 요인으로 작용하며, C. polykrikoides 적조는 해양에서 증가한 암모니아질소 농도와 연관되는 것으로 나타났다. In the 1990s, Cochlodinium polykrikoides red tide has been annually occurred in the southern coast of Korea and caused the mass damage to the fisheries with a huge amount of economic loss. The present study was done to establish the biological foundation for the elucidation of the mechanism of C. polykrikoides red tide. The growth response of C. polykrikoides to physico-chemical factors such as temperature, salinity, pH, and light intensity were examined using axenic cultures to evaluate the relative importance of these factors on the dynamics of natural populations. It was found that the highest growth conditions were 25℃, 40‰, pH 7.5, and 7,500lux, respectively. The tolerable salinity range of growth was relatively wide at an optimum temperature and was reduced to a much narrower range at a sub-optimum temperature. These findings indicate that C. polykrikoides is an eurythermal and euryhaline organism. The organism demanded higher light intensity and oceanic pH narrow in its growth. C. polykrikoides utilize inorganic nutrients, such as nitrate and ammonium as N, and phosphate as P. The nutritional requirements of C. polykrikoides were 40㎛ for nitrate, 50 ㎛ for ammonium, and 5 ㎛ for phosphate. The half saturation constant (Ks) for growth was 2.10 ㎛ for nitrate, 1.03 ㎛ for ammonium, and 0.57㎛ for phosphate. These values were comparatively smaller than those of other dinoflagellates reported previously. We confirmed that the organism is characterized as an eutrophic species. However, ammonium Ks value is smaller than that of other eutrophic species. This result indicates that C. polykrikoides red tide may outbreak in the waters which eutrophication is in progress rather than eutrophicated waters. C. polykrikoides preferred ammonium better than nitrate as a nitrogen source when in a growth stage. Therefore, our results indicate that ammonium is more important nutrient on the growth of the organism in comparison with other inorganic nutrients and C. polykrikoides red tide is related with the increased ammonium concentration in the coastal waters.

수직-수평온도구배법에 의한 200 mm급 사파이어 단결정 성장의 전산모사 연구

김형중 ( Hyung Joong Kim ),차필령 ( Pil Ryung Cha ),김성균 ( Seong Gyoon Kim ),문성환 ( Sung Hwan Moon ),장계원 ( Gye Won Jang ),나복기 ( Bok Kee Na ),김준환 ( Jun Hwan Kim ),김동욱 ( Dong Uk Kim ) 대한금속재료학회(구 대한금속학회) 2015 대한금속·재료학회지 Vol.53 No.1

A sapphire single crystal growth process by the Vertical-Horizontal Gradient Freezing (VHGF) method was studied by a numerical analysis technique. The heater power was controlled in order to follow the given arbitrary target heater temperature profile through the whole series of the process. Due to the influence of radiation heat transfer, the heater had spatial temperature deviation in spite of the fact that the heater power was imposed uniformly through its whole body. As a structural feature of the VHGF method, temperature at the lower part of crucible was lower than that at the upper part of crucible because it was cooler at the bottom of the furnace. Thus, the movement of the solid/liquid interface was driven in the bottom-to-top direction. (Received February 4, 2014)

조류성장잠재력 시험에 의한 사량도 연안 Cochlodinium polykrikoides 적조의 제한영양염

김형철(Hyung Chul Kim),김동명(Dong Myung Kim),이대인(Dae In Lee),박청길(Chung Kil Park),김학균(Hak Gyoon Kim) 한국수산과학회 2001 한국수산과학회지 Vol.34 No.5

우리나라 남해안에서 매년 유해 와편모조류인 Cochlodinium polykrikoides에 의한 적조가 발생하고 있는데, 본 연구에서는 남해안의 사량도 주변 해역을 대상으로 AGP 시험을 통하여 C. polykrikoides의 성장 제한영양염을 평가하였다. Macro- 및 micro-nutrients 첨가에 의한 적조 발생 단계별 C. polykrikoides의 성장은 두 가지의 서로 다른 반응으로 나타나 조류성장 제한영양염이 명확하게 확인되었다. 사량도 해역의 고정점에서 적조가 발생하기 전인 7월과 8월, 적조가 소멸한 후인 10월의 AGP 시험에서는 질산질소 (50 ㎛)와 인산인 (5 ㎛), 암모니아 질소 (50 ㎛)와 인산인 (5 ㎛)의 복합첨가에 의해 성장률이 크게 증가하였다. Macro-nutrients의 단일첨가에 대해서는 뚜렷한 성장을 나타내지 않았고 micro-nutrients도 성장을 촉진시키지 않았다. 이러한 결과로 이 시기에는 질소와 인이 동시에 C. polykrikoides의 성장 제한영양염으로 작용하였다는 것이 확인되었다. 그러나, 적조가 발생한 9월의 AGP 시험에서는 성장에 필요한 macro- 및 micro-nutrients의 결핍이 나타나지 않아 이 기간 중에 C. polykrikoides의 성장은 영양염의 제한을 받지 않는다는 것이 확인되었다. 이때 사량도 연안의 영양염 농도는 암모니아질소와 인산인 농도가 각각 24.33, 1.61 ㎛로 적조가 발생하기 전과 소멸한 후에 비해 평균 8.2, 4.8배 높은 값을 나타냈고, 질산질소 농도는 0.58 ㎛로 평균 3.3배 낮은 값을 나타냈다. 그러므로, C. polykrikoides 적조는 N, p 농도 증가에 기인한 부영양화가 진행되는 해역에서 발생할 가능성이 높다는 것을 시사한다. Algal growth potential (AGP) assay using Cochlodinium polykrikoides was conducted in Saryang Island coast where C. polykrikoides red tide occurred annually from July to October 1998. The effects of macro- and micro-nutrients on the growth of C. polykrikoides were specfically evaluated by the algal assay method. Two different types of growth response of C. polykrikoides for the addition of nutrients were clearly observed. For both before and after C, polykrikoides occurrence, the growth of C. polykrikoides was significantly stimulated by the addition of either nitrate or ammonium of 50 ㎛ with phosphate of 5 ㎛. The addition of a single nutrient had no clear effect on the growth of C. polykrikoides and the addition of trace metals, vitamins, and EDTA etc. did not stimulate the algal growth, also. This result indicates that both N and P potentially limited the growth of C. polykrikoides in this period. However, during a bloom of C. polykrikoides, the growth was unlikely to be stimulated by the addition of both macro- and micro-nutrients. At that time, the nutrient concentration of Saryang Island coast was 24.33 ㎛ for ammonium, 1.61 ㎛ for phosphate, and 0.58 ㎛ for nitrate, respectively. The concentrations of nutrients increased, on average, 8.2-fold for ammonium and 4.8-fold for phosphate, decreased 3.3-fold for nitrate compared to both before and after the red tide. This result shows that the growth of C. polykrikoides was not limited by the nutrients during the bloom in September. Therefore, our results suggest that the C. polykrikoides red tide may outbreak especially when the water is fertilized due to the increased N and P.

일가족에 발생한 골화석증

최웅송(Oung Seung Choi),박정영(Jong Young Park),이배진(Bai Jin Lee),이정호(Jung Ho Lee),김형기(Hyung Gi Kim),최낙현(Nak Hyun Choi),박봉수(Bong Sou Park),김시찬(Si Chan Kim),변동일(Dong Il Byun),김형길(Hyung Gil Kim),정동균(Dong Gyoon 대한내과학회 1994 대한내과학회지 Vol.47 No.6

N/A Osteopetrosis (also called Albers-Schoberg's disease, Marble bones and chalk bones) is a rare hone dysplasia in which, on the basis of a failure of osteoclastic and chondroclastic resorption, the bone become exceedingly dense. Two clinically distinct forms are now recognized and have different patterns of inheritance. The milder form is transmitted as an autosomal dominant trait and the more severe form is transmitted as an autosomal recessive trait. We have experienced a familial osteopertrosis, mother and three siblinges out of six, which was thought to be a autosomal dominant inheritance. We report a case of milder form of osteopetrosis with a review of literature.

Mid-infrared luminosity function of local star-forming galaxies in the North Ecliptic Pole-Wide survey field of<i>AKARI</i>

Kim, Seong Jin,Lee, Hyung Mok,Jeong, Woong-Seob,Goto, Tomotsugu,Matsuhara, Hideo,Im, Myungshin,Shim, Hyunjin,Kim, Min Gyu,Lee, Myung Gyoon Oxford University Press 2015 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.454 No.2

THE 3.3 μm POLYCYCLIC AROMATIC HYDROCARBON EMISSION AS A STAR FORMATION RATE INDICATOR

Kim, Ji Hoon,Im, Myungshin,Lee, Hyung Mok,Lee, Myung Gyoon,Jun, Hyunsung David,Nakagawa, Takao,Matsuhara, Hideo,Wada, Takehiko,Oyabu, Shinki,Takagi, Toshinobu,Inami, Hanae,Ohyama, Youichi,Yamada, Rika IOP Publishing 2012 The Astrophysical journal Vol.760 No.2

<P>Polycyclic aromatic hydrocarbon (PAH) emission features dominate the mid-infrared spectra of star-forming galaxies and can be useful to calibrate star formation rates (SFRs) and diagnose ionized states of grains. However, the PAH 3.3 mu m feature has not been studied as much as other PAH features since it is weaker than others and resides outside of Spitzer capability. In order to detect and calibrate the 3.3 mu m PAH emission and investigate its potential as an SFR indicator, we carried out an AKARI mission program, AKARI mJy Unbiased Survey of Extragalactic Sources (AMUSES), and compared its sample with various literature samples. We obtained 2-5 mu m low-resolution spectra of 20 flux-limited galaxies with mixed spectral energy distribution classes, which yielded the detection of the 3.3 mu m PAH emission from 3 out of 20 galaxies. For the combined sample of AMUSES and literature samples, the 3.3 mu m PAH luminosities correlate with the infrared luminosities of star-forming galaxies, albeit with a large scatter (1.5 dex). The correlation appears to break down at the domain of ultraluminous infrared galaxies (ULIRGs), and the power of the 3.3 mu m PAH luminosity as a proxy for the infrared luminosity is hampered at log[L-PAH3.3 erg(-1) s(-1)] > similar to 42.0. Possible origins for this deviation in the correlation are discussed, including contributions from active galactic nuclei and strongly obscured young stellar objects, and the destruction of PAH molecules in ULIRGs.</P>

THE <i>AKARI</i> 2.5-5.0 μm SPECTRAL ATLAS OF TYPE-1 ACTIVE GALACTIC NUCLEI: BLACK HOLE MASS ESTIMATOR, LINE RATIO, AND HOT DUST TEMPERATURE

Kim, Dohyeong,Im, Myungshin,Kim, Ji Hoon,Jun, Hyunsung David,Woo, Jong-Hak,Lee, Hyung Mok,Lee, Myung Gyoon,Nakagawa, Takao,Matsuhara, Hideo,Wada, Takehiko,Oyabu, Shinki,Takagi, Toshinobu,Ohyama, Youic IOP Publishing 2015 The Astrophysical journal Supplement series Vol.216 No.1

<P>We present 2.5-5.0 mu m spectra of 83 nearby (0.002 <z <0.48) and bright (K <14 mag) type-1 active galactic nuclei (AGNs) taken with the Infrared Camera on board AKARI. The 2.5-5.0 mu m spectral region contains emission lines such as Br alpha (2.63 mu m), Bra (4.05 mu m), and polycyclic aromatic hydrocarbons (3.3 mu m), which can be used for studying the black hole (BH) masses and star formation activity in the host galaxies of AGNs. The spectral region also suffers less dust extinction than in the ultra violet (UV) or optical wavelengths, which may provide an unobscured view of dusty AGNs. Our sample is selected from bright quasar surveys of Palomar-Green and SNUQSO, and AGNs with reverberation-mapped BH masses from Peterson et al. Using 11 AGNs with reliable detection of Brackett lines, we derive the Brackett-line-based BH mass estimators. We also find that the observed Brackett line ratios can be explained with the commonly adopted physical conditions of the broad line region. Moreover, we fit the hot and warm dust components of the dust torus by adding photometric data of SDSS, 2MASS, WISE, and ISO to the AKARI spectra, finding hot and warm dust temperatures of similar to 1100K and similar to 220 K, respectively, rather than the commonly cited hot dust temperature of 1500 K.</P>

Fe40Ni40P14B6 비정질합금에서 결정의 핵생성기구 (2)

김성균,나형용 대한금속재료학회(대한금속학회) 1989 대한금속·재료학회지 Vol.27 No.12

The nucleation rate with temperature and time during crystallization of Fe_(40)Ni_(40) P_(14)B_6 metallic glass investigated in the preceding paper( I ) was discussed quantitatively using the classical homogeneous nucleation theory. The diffusion coefficient, glass-crystal interface energy(σ) and dσ/dT(T : temperature) obtained from the non-steady state homogeneous nucleation theory agree well with the reported values, which means that the nonsteady state homogeneous nucleation occurs during crystallization. We also showed that the glass-crystal interfacial energy in this alloy must decrease with temperature and discussed the exponent n of Johnson-Mehl-Avrami equation.