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      • KCI등재

        계면활성제 함유 인지질 나노입자의 초가변성 연구

        신지영,오유경,강민정,권경애,김종국 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.3

        This study was aimed to formulated various phospholipid nanoparticles composed of different surfactants and to evaluate the deformability of the phospholipid vesicles as candidates of useful ultradeformable nanoparticles. In vitro deformability of the hospholipid nanoparticles was studied using an extruder under a certain pressure. The sizes of phospholipid nanoparticles, passed volumes, and concentrations of the phospholipids in suspensions before and after extrusion were measured. The deformability indexes were estimated by using passed volumes, sizes of phospholipid nanoparticles and concentrations of phospholipids. Conventionl liposomes, placed under a certain pressure of an extruder, showed no passed volume indicating little deformability. Similar to conventional liposomes, phospholipid nanoparticles containing surpactants such as sodium taurcholate, Myrj 45, or Myrj 53 showed little deformability. In contrast, phospholipid nanoparticles composed of Tween 20, triton X-100, or sodium deoxycholate showed higher deformability indexes than others. Taken together, the deformability of phospholipid nanoparticles could be significantly affected by the type of surfactants. Moreover, these results suggest that the deformability of phospholipid nanoparticles could be modulated by surfactants.

      • 반응성 DC sputtering법으로 제조한 AIN박막의 수소첨가효과

        김지균,김민석,권정열,이헌용 明知大學校 産業技術硏究所 2000 産業技術硏究所論文集 Vol.19 No.-

        In GaAs devices, the development of a finer insulator instead of SiO₂to be used the insulator of Si has been made good progress. That, however, is not to be enough. We studied the development of the finer insulator in GaAs devices. The AIN has the characteristics of thermal stability over 2400℃ and resistivity over 10 13 Ω, and superior insulator characteristic to have rate of thermal expansion(a=4.2x10 -6, b=5.3x10 -6/K) similar with SiO₂and GaAs. An AIN has been evaluated good applied insulator for above characteristics in chemical compound. Then, the purpose of this paper is a development of MIS devices using AIN as an insulator, and is to investigate a electrical characteristic changing by H₂addition to AIN. The ratio of H₂addition was established by 5%. The pressure was maintained by 5 mTorr and the DC power was supplied by 150W during the experiment. The H₂addition to AIN may have an effect on diminishing impurities on surface and improves the properties as an insulator to a MIS structures.

      • KCI등재

        혈구세포 수송체로 투여된 트레일 유전자의 혈중 발현 지속 효과

        변향민,권경애,신지영,오유경 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.4

        Tumor necrosis factor-related apoptosis -inducing ligand (TRAIL) is a recently identified member of the tumor necrosis factor cytokine superfamily. TRAIL has been shown to induce apoptosis in a number of tumor cells whereas cells from most of normal tissues are highly resistant to TRAIL-induced apoptosis. These observations have raised considerable interest in the use of TRAIL in tumor therapy. In this study we report the biodistribution fates and serum expression pattern of plasmid DNA encoding TRAIL (pTRAIL) delivered in erythrocyte ghosts(EG). pTRAIL was loaded into EG by electroporation in a hypotonic medium. The mRNA expression of pTRAIL was prolonged following delivery in EG-encap-sulated forms. EG containing pTRAIL showed significant levels of mRNA expression in the blood over 9 days. The organ expression patterns of pTRAIL delivered via EG, however, did not significantly differ from those of naked pTRAIL, indicating that the expression-enhancing effect of EG containing pTRAIL, was localized to the blood. These results suggest that pTRAIL-loaded EG might be of potential use in the treatment of hematological diseases such as TRAIL-sensitive leukemia.

      • KCI등재후보

        Escherichia coli 패혈증 환자에 합병된 대칭적 하지 말단 괴사증 1예

        남해성,유진홍,권순석,민준기,조현선,박민경,심병주,남유정,이지인,김진수,길욱현,조근종,신완식 대한감염학회 2005 감염과 화학요법 Vol.37 No.6

        We have encountered a rare case of symmetrical peripheral gangrene complicating Escherichia coli sepsis in a 47-years-old male. He was successfully treated with antibiotics, anticoagulants, and vasodilator. To our knowledge, this is the first report on symmetrical peripheral gangrene complicating E. coli sepsis in Korea.

      • Prevalence and associations for abnormal bleeding times in patients with renal insufficiency

        Kim, Ha Yeon,Oak, Chan Young,Kim, Min Jee,Kim, Chang Seong,Choi, Joon Seok,Bae, Eun Hui,Ma, Seong Kwon,Kim, Soo Wan Informa UK, Ltd. 2013 Platelets Vol.24 No.3

        <P>Platelet dysfunction and associated hemorrhagic complications are often encountered in patients with chronic kidney disease. This study aimed to evaluate the prevalence and associations for abnormal bleeding time (BT) in patients with renal dysfunction. Hemoglobin, hematocrit, platelet, blood urea nitrogen, creatinine, and parathyroid hormone levels were determined in 1716 patients (55.18 ± 17.19 years, men 50.8%). For these patients, BTs were estimated using a platelet function analyzer-100. Glomerular filtration rates (GFRs) were estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. The study population was divided into six groups according to the estimated GFR (eGRF): group I, eGFR ≥ 90 ml/min/1.73 m<SUP>2</SUP>; group II, 60 ≤ eGFR < 90 ml/min/1.73 m<SUP>2</SUP>; group III, 30 ≤ eGFR < 60 ml/min/1.73 m<SUP>2</SUP>; group IV, 15 ≤ eGFR < 30 ml/min/1.73 m<SUP>2</SUP>; group V, eGFR < 15 ml/min/1.73 m<SUP>2</SUP>; and group VI, undergoing regular hemodialysis. Renal insufficiency was defined as eGFR < 60 ml/min/1.73 m<SUP>2</SUP>. To further investigate the role of inflammatory cytokines, nitric oxide (NO) and tumor necrosis factor alpha (TNF-&agr;) were measured in a 327-patient subset of the total patient population (52.82 ± 18.3 years, men 60.9%). Abnormal BT occurred in 11.8% of group I, 15.3% of group II, 29.1% of group III, 37.5% of group IV, 35.0% of group V, and 32.1% of group VI. By Pearson correlation coefficient, eGFR (<I>r</I> = −0.089), hemoglobin (<I>r</I> = −0.127), platelet (<I>r</I> = −0.054) were correlated with BT. Multivariate analysis revealed that age [odds ratio (OR), 1.013; 95% CI, 1.004-1.022], renal insufficiency (eGFR < 60 ml/min/1.73 m<SUP>2</SUP>; OR, 2.271; 95% CI, 1.672-3.083), anemia (hemoglobin < 120 g/l; OR, 1.486; 95% CI, 1.089-2.027), and thrombocytopenia (platelet < 150 × 10<SUP>9</SUP>/l; OR, 1.445; 95% CI, 1.089-1.918) were independently associated with prolonged BT. Plasma levels of NO and TNF-&agr; were increased in patients with renal insufficiency (eGFR < 60 ml/min/1.73 m<SUP>2</SUP>). Plasma levels of NO in renal insufficiency group were higher in prolonged BT than those in normal BT. A significant positive correlation was noted between BTs and NO levels (<I>r</I> = 0.152, <I>p</I> = 0.009) but not with TNF-&agr; levels. The prevalence of abnormal BTs was higher as eGFR declined. Old age, renal insufficiency, anemia, and thrombocytopenia were independent associations for abnormal BT.</P>

      • SCIESCOPUSKCI등재

        Differential Effects of Typical and Atypical Antipsychotics on MK-801-induced EEG Changes in Rats

        Kwon, Jee-Sook,Kim, Ki-Min,Chang, Su-Min,Kim, Choong-Young,Chung, Tai-Ho,Choi, Byung-Ju,Lee, Maan-Gee The Korean Society of Pharmacology 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.1

        We examined whether the abnormal EEG state by NMDA receptor blocker MK-801 can be reversed by typical and atypical antipsychotics differentially by comparing their spectral profiles after drug treatment in rats. The spectral profiles produced by typical antipsychotics chlorpromazine (5 mg/kg, i.p.) and haloperidol (0.5 mg/kg, i.p.) were differ from that by atypical antipsychotic clozapine (5 mg/kg, i.p.) in the rats treated with or without MK-801 treatment (0.2 mg/kg, i.p.) which produce behavioral abnormalities like hyperlocomotion and stereotypy. The dissimilarity between the states produced by antipsychotics and the control state was examined with the distance of the location of the canonical variables calculated by stepwise discriminant analysis with the relative band powers as input variables. Although clozapine produced more different state from normal state than typical antipsychotics, clozapine could reverse the abnormal schizophrenic state induced by MK-801 to the state closer to the normal state than the typical antipsychotics. The results suggest that atypical anesthetic can reverse the abnormal schizophrenic state with negative symptom to the normal state better than typical antipsychotic. The results indicate that the multivariate discriminant analysis using the spectral parameters can help differentiate the antipsychotics with different actions.

      • KCI등재

        Epigenetic Changes in Neurodegenerative Diseases

        Kwon, Min Jee,Kim, Sunhong,Han, Myeong Hoon,Lee, Sung Bae Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.11

        Afflicted neurons in various neurodegenerative diseases generally display diverse and complex pathological features before catastrophic occurrence of massive neuronal loss at the late stages of the diseases. This complex nature of neuronal pathophysiology inevitably implicates systemwide changes in basic cellular activities such as transcriptional controls and signal cascades, and so on, as a cause. Recently, as one of these systemwide cellular changes associated with neurodegenerative diseases, epigenetic changes caused by protein toxicity have begun to be highlighted. Notably, recent advances in related techniques including next-generation sequencing (NGS) and mass spectrometry enable us to monitor changes in the post-translational modifications (PTMs) of histone proteins and to link these changes in histone PTMs to the specific transcriptional changes. Indeed, epigenetic alterations and consequent changes in neuronal transcriptome are now begun to be extensively studied in neurodegenerative diseases including Alzheimer's disease (AD). In this review, we will discuss details of our current understandings on epigenetic changes associated with two representative neurodegenerative diseases [AD and polyglutamine (polyQ) diseases] and further discuss possible future development of pharmaceutical treatment of the diseases through modulating these epigenetic changes.

      • Coiled-coil structure-dependent interactions between polyQ proteins and Foxo lead to dendrite pathology and behavioral defects

        Kwon, Min Jee,Han, Myeong Hoon,Bagley, Joshua A.,Hyeon, Do Young,Ko, Byung Su,Lee, Yun Mi,Cha, In Jun,Kim, Seung Yeol,Kim, Dong Young,Kim, Ho Min,Hwang, Daehee,Lee, Sung Bae,Jan, Yuh Nung National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.45

        <P><B>Significance</B></P><P>It remains unclear how the structural properties of polyglutamine (polyQ) proteins, which underlie several neurodegenerative disorders, including Huntington’s disease and spinocerebellar ataxias (SCAs), translate into the toxicity of these proteins. Here, we demonstrate that coiled-coil structures in expanded polyQ regions of SCA type 3 (SCA3) proteins cause dendrite defects in <I>Drosophila</I> neurons, as well as behavioral abnormalities. Moreover, interactions of SCA3 with Foxo mediated by coiled-coil domains of these two proteins resulted in functional impairment of this transcription factor, whereas its overexpression significantly rescued the SCA3-induced defects. Our study expanded the current understanding of neuronal pathology mediated by polyQ proteins via the coiled-coil–mediated interactions. These results may have important implications in therapeutic strategies for polyQ protein-related diseases.</P><P>Neurodegenerative disorders, such as Huntington’s diseases and spinocerebellar ataxias (SCAs), are driven by proteins with expanded polyglutamine (polyQ) tracts. Recently, coiled-coil structures in polyQ regions of such proteins were shown to facilitate aggregate formation and ultimately lead to cell death. However, the molecular mechanism linking these structural domains to neuronal toxicity of polyQ proteins remains elusive. Here, we demonstrate that coiled-coil structures in the Q repeat region of SCA type 3 (SCA3) polyQ proteins confer protein toxicity in <I>Drosophila</I> neurons. To functionally characterize coiled-coil structures in the Q repeat regions, we generated three structural variants of SCA3 polyQ proteins: (<I>i</I>) MJDtr-76Q, containing both α-helical coiled-coil and β-sheet hairpin structures in the Q repeat region; (<I>ii</I>) MJDtr-70Q_cc0, possessing only α-helical coiled-coil structures due to the incorporation of β-sheet–breaking residues (Q-to-N or Q-to-E mutations); and (<I>iii</I>) MJDtr-70Q_pQp, with no secondary structure due to the introduced proline residues (Q-to-P mutations). Through comparative analysis of these variants, we found that coiled-coil structures facilitated nuclear localization of SCA3 polyQ proteins and induced dendrite defects in <I>Drosophila</I> dendritic arborization neurons. Furthermore, genetic and functional screening identified the transcription factor Foxo as a target of polyQ proteins, and coiled-coil–mediated interactions of Foxo and polyQ proteins in the nucleus resulted in the observed dendrite and behavioral defects in <I>Drosophila</I>. These results demonstrate that coiled-coil structures of polyQ proteins are crucial for their neuronal toxicity, which is conferred through coiled-coil to coiled-coil interactions with the nuclear targets of these proteins.</P>

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