[Show abstract][Hide abstract] ABSTRACT: The ligand for CD137 (CD137L; also called 4-1BBL) is mainly expressed on activated APCs such as dendritic cells, B cells and macrophages. Even though CD137L functions as a trigger of the CD137 signaling pathway for T cell activation and expansion, engagement of CD137L can deliver a signal leading to the production of proinflammatory cytokines in macrophages.
We generated cell-permeable TAT-CD137L cytoplasmic domain fusion protein (TAT-CD137Lct) and examined its ability to initiate the CD137L reverse signaling pathway.
Treatment of TAT-CD137Lct induced the production of high levels of IL-6 and TNF-α mRNAs and proteins in peritoneal macrophages. TAT-CD137Lct increased phosphorylation of Erk, p38 MAPK and Jnk, and activated transcription factors C/EBP and CREB. However, TAT-CD137Lct did not visibly affect the degradation of the inhibitor of NF-kB (IkBα). We further demonstrated that JNK activation was required for TAT-CD137Lct-induced production of TNF-α, while activation of Erk and p38 MAPK were involved in IL-6 and TNF-α production.
Our results suggest that TAT-CD137Lct is an effective activator for the CD137L reverse signaling pathway.
[Show abstract][Hide abstract] ABSTRACT: Pigmented mammary Paget disease (PMPD) is a rare subtype of mammary Paget disease that presents as a hyperpigmented patch or plaque over the areola and nipple. We herein report on an unusual case of PMPD with reticulated features in a 98-year-old female. The histology showed intraepidermal pagetoid cells containing melanin pigments without any underlying intraductal carcinoma.
Annals of Dermatology 02/2011; 23(1):73-5. DOI:10.5021/ad.2011.23.1.73 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of this investigation was to evaluate the effects of structural differences between FIAU and FIRU on their ability to serve as a potential tracer for reporter gene imaging. To examine the characteristics of different configurations of FIAU and FIRU, a series of evaluations were done on HSV1-TK gene-expressing cells and on mice with HSV1-TK gene-expressing tumor. The results showed that, as an imaging agent for HSV1-TK-expressing cells, radiolabeled FIAU was more efficient for in vivo imaging than FIRU.
Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine 06/2010; 68(6):971-8. DOI:10.1016/j.apradiso.2009.12.032 · 1.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Focal acral hyperkeratosis (FAH) is a rare genodermatosis with an autosomal dominant pattern of inheritance; however, it may also be sporadic. FAH is characterized by late-onset crateriform keratotic papules, some coalescing into plaques, along the borders of the hands and feet. We herein report a case of FAH in a 47-year-old male with a family history of similar lesions in three generations. The histological findings revealed focal areas of orthohyperkeratosis over an area of depressed but otherwise normal epidermis. The dermis showed no specific changes, which distinguished this case from acrokeratoelastoidosis, which shows elastorrhexis of clinically similar lesions.
Annals of Dermatology 11/2009; 21(4):426-8. DOI:10.5021/ad.2009.21.4.426 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to investigate Korean children’s environmental literacy levels and the variables that affect their environmental literacy. An instrument, the Environment Literacy Instrument for Korean Children (ELIKC), was developed that measures four different dimensions (knowledge, attitude, behaviour, and skills) using 69 items and 13 demographic variables. The ELIKC was administered to 969 Year 3 students from large cities, medium‐sized cities, and rural areas. The students were given 80 min to answer the questions. Statistical analysis was performed on each of the scales that make up the ELIKC and a multivariate analysis of variance was performed to identify the variables that affect environmental literacy. Results indicate that the correlation between attitude and behaviour is the strongest while that between knowledge and behaviour is the weakest. Also, it was found that gender, parents’ school background, and the source from where students obtain environmental information affect all categories of environmental literacy.
International Journal of Science Education 05/2007; 29(6):731-746. DOI:10.1080/09500690600823532 · 1.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to examine Korean elementary teachers' understanding of creativity, in particular those who teach the gifted students. Facilitating creativity was one of the major goals in gifted education in Korea, and teachers' role was considered to be crucial in achieving this goal. Forty-two elementary teachers were surveyed with an open-ended questionnaire to identify their understanding of creativity. Their answers were analyzed based on cognitive, personal, and environmental components of creativity. Teachers who mentioned all three components were recognized to have a balanced view. However, one third of the teachers had a biased view, mentioning only I component. Many had air intermediate view, mentioning 2 components. Preference for tire cognitive component, the disregard of the personal component, and the partial understanding of the environmental component were also discovered. To successfully facilitate creativity in gifted education, teachers' balanced view is essential. Thus the personal component and the environmental component should be emphasized to improve their understanding.
Creativity Research Journal 04/2006; 18(2):237-242. DOI:10.1207/s15326934crj1802_9 · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Motor complications after chronic L-3,4-dihydroxyphenylalanine (L-DOPA) therapy occur partly because of the sensitization to dopaminergic agents resulting from pulsatile dopaminergic stimulation. The loss of presynaptic storage contributes to short duration of action by dopamine. Vesicular monoamine transporter-2 (VMAT-2) controls intraneuronal dopamine storage by packaging dopamine into synaptic vesicles, thereby allowing exocytotic release of dopamine. Using primary fibroblast doubly transduced with VMAT-2 and aromatic L-amino acid decarboxylase (AADC) genes, we previously demonstrated the beneficial effects of such double gene transduction in the production, storage, and gradual release of dopamine in vitro and in vivo. In this study, we further evaluate the effect of achieving sustained level of dopamine within the striata by VMAT-2 gene on behavioral response of parkinsonian rats after chronic intermittent L-DOPA administration. Primary fibroblast (PF) cells were genetically modified with AADC and VMAT-2 genes. We grafted primary fibroblast cells, PF with AADC (PFAADC), or doubly transduced PF with AADC and VMAT-2 (PFVMAA) (n = 6 for each group) into parkinsonian rat striata and administered L-DOPA (25 mg/kg/day) intermittently for 4 weeks. For behavioral study, we employed a model of akinesia using forepaw adjusting steps (FAS) that have been well characterized to reflect the effect of the lesion and the antiparkinsonian effect of dopaminergic drugs and transplants. The duration of FAS response to L-DOPA was sustained for a longer duration in rats grafted with PFVMAA cells than in those grafted with either control cells or cells with AADC alone. In PFVMAA-grafted animals, prolonged duration of FAS responses to L-DOPA was sustained even 6 weeks after discontinuation of 4-week intermittent L-DOPA treatment. These findings suggest that the restoration of dopamine storage capacity could enhance the efficacy of L-DOPA therapy and attenuate the motor fluctuations that result from chronic intermittent L-DOPA administration. The gene therapy expressing AADC and VMAT-2 along with systemic L-DOPA therapy could provide a novel treatment strategy to prevent motor fluctuations.
[Show abstract][Hide abstract] ABSTRACT: Hyaluronic acid (hyaluronan, HA) was immobilized onto the surface of macroporous biodegradable poly(D,L-lactic acid-co-glycolic acid) [PLGA] scaffolds to enhance the attachment, proliferation, and differentiation of chondrocytes for cartilage tissue engineering. The PLGA scaffolds were prepared by blending PLGA with varying amounts of amine-terminated PLGA-PEG di-block copolymer. They were fabricated by a gas foaming/salt leaching method. HA was chemically conjugated to the surface-exposed amine groups on the pre-fabricated scaffolds. The amount of surface exposed free amine groups was quantitatively determined by conjugating an amine-reactive fluorescent dye to the PLGA blend films. The extent of HA immobilization was also confirmed by measuring water contact angles. When chondrocytes were seeded within HA modified PLGA scaffolds, enhanced cellular attachment was observed compared to unmodified PLGA scaffolds. Furthermore, glycosaminoglycan and total collagen synthesis increased substantially for HA modified PLGA scaffolds. RT-PCR result and histological examination of the resultant cartilage tissue revealed that HA modified scaffolds excelled in inducing cartilage tissue formation in terms of collagen type II expression and tissue morphological characteristics.
[Show abstract][Hide abstract] ABSTRACT: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in remodeling of extracellular matrix (ECM) in the glomeruli. PAI-1 is up-regulated by high glucose and is overexpressed in diabetic kidney. Since reactive oxygen species (ROS) mediate ECM accumulation in diabetic glomeruli and was recently found to mediate transforming growth factor-beta1 (TGF-beta1)-induced PAI-1 up-regulation in glomerular mesangial cells, we examined the role of ROS in high glucose-induced PAI-1 expression in cultured glomerular mesangial cells and in streptozotocin-induced diabetic rat glomeruli.
Growth arrested and synchronized primary rat mesangial cells were treated with different concentrations of glucose in the presence or absence of N-acetylcysteine (NAC) or trolox, or after cellular reduced form of glutathione (GSH) depleted with DL-buthionine-(S,R)-sulfoximine (BSO). Taurine was administered to diabetic rats from 2 days to 4 weeks after streptozotocin injection. Urinary protein excretion, glomerular volume, and fractional mesangial area were measured as markers of renal injury and lipid peroxide (LPO) as an oxidative stress marker. PAI-1 mRNA expression was measured by Northern blot analysis in mesangial cells and reverse transcription-polymerase chain reaction (RT-PCR) in glomeruli, PAI-1 protein by Western blot analysis and enzyme-linked immunosorbent assay (ELISA), and plasmin activity by fluorometry.
High glucose significantly increased PAI-1 mRNA and protein expression and decreased plasmin activity in mesangial cells. Equimolar concentrations of l-glucose or mannitol did not affect PAI-1 expression. BSO pretreatment significantly increased basal PAI-1 expression and amplified the response to high glucose. NAC effectively inhibited high glucose-induced, but not basal, PAI-1 expression. Reduced plasmin activity in mesangial cells by high glucose was rescued by antioxidants. Anti-TGF-beta antibody inhibited both high glucose- and H(2)O(2)-induced PAI-1 up-regulation. Taurine significantly reduced plasma LPO, glomerular PAI-1 expression, glomerular volume, fractional mesangial area, and proteinuria in streptozotocin-induced diabetic rats.
These results demonstrate that ROS mediate high glucose-induced up-regulation of PAI-1 expression in cultured mesangial cells and in diabetic glomeruli. Since both high glucose and TGF-beta1 induce cellular ROS and ROS mediate both high glucose- and TGF-beta1-induced PAI-1, ROS appear to amplify TGF-beta1 signaling in high glucose-induced PAI-1 up-regulation. Antioxidants can prevent accumulation of ECM protein in diabetic glomeruli partly by abrogating up-regulation of PAI-1 and suppression of plasmin activity.
Kidney International 06/2005; 67(5):1762-71. DOI:10.1111/j.1523-1755.2005.00274.x · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: With the passing of Korea's Gifted Education Act, creativity has come to the forefront in considering the future of Korea's economic prosperity in the global economy (Korean Educational Development Institute, 2003). The purpose of this study was to examine the understanding of creativity among Korean science teachers of gifted students. Sixty teachers participated in this study with an open-ended questionnaire about their understanding of creativity. The data were analyzed based on Urban's (1995) three components of creativity. The findings indicated that these science teachers had a thorough understanding of the cognitive component and a strong association of creativity with intellectual ability, but overidentified with the cognitive component, showing less awareness of the personal and environmental components of creativity. To shift their understanding to a more balanced view, personality and environmental components, as well as attributes in other component areas, should be emphasized.
[Show abstract][Hide abstract] ABSTRACT: Some abnormal findings in routine MRI have been proposed as helpful discriminators for distinguishing multiple system atrophy (MSA) from Parkinson's disease (PD). However, what the most distinguishing MRI findings for MSA-p (parkinsonism dominant) or MSA-c (cerebellar dominant) are separately has not been systematically analyzed. To determine what the most helpful discriminators for MSA-p or MSA-c are and whether those findings are correlated with the presence of parkinsonism or cerebellar dysfunction, we compared 10 previously reported MRI findings in 36 patients with probable MSA-p, 27 patients with probable MSA-c and 30 patients with PD separately. In our results, hyperintense rim and putaminal atrophy among supratentorial parameters and the parameters of infratentorial atrophy were significantly prominent in MSA-p comparing to PD. Hyperintense rim showed the highest specificity in MSA-p patients (90.0%) with relatively suboptimal sensitivity (72.2%). In MSA-c, all infratentorial parameters had strong discriminating power comparing to PD. Signal increase in the middle cerebellar peduncle showed the highest specificity (100%) and had fair sensitivity (85.2%) in MSA-c. Compared between MSA-p and MSA-c, supratentorial parameters were not valid to differentiate MSA-c from MSA-p except for putaminal atrophy. On the contrary, infratentorial parameters were good for distinguishing MSA-c from MSA-p except dilatation of the fourth ventricle. Parkinsonism was not correlated with a hyperintense rim, but cerebellar symptoms were correlated with signal increase in the middle cerebellar peduncle. Our findings suggest the characteristic MRI can be helpful for differentiating MSA-p and MSA-c from PD, respectively, although they do not reflect the presence or lateralization of parkinsonism.
[Show abstract][Hide abstract] ABSTRACT: Chronic L-3,4-dihydroxyphenylalanine (L-DOPA) therapy in Parkinson's disease (PD) is complicated by motor response fluctuations and dyskinesia. The relative contributions of disease severity and chronic L-DOPA therapy to the development of motor fluctuation are not well defined clinically. Experimental studies have been limited partly because models for the antiparkinsonian effects on akinesia have not been employed. Therefore, we employed a model of akinesia using forepaw adjusting steps that have been well characterized to reflect the effect of lesions and the antiparkinsonian effect of dopaminergic drugs and transplants. We administered L-DOPA (12.5 mg/kg) intermittently for 4 weeks to rats with severe nigrostriatal lesions produced by injecting 6-hydroxydopamine into the medial forebrain bundle. The peak magnitude responses to L-DOPA increased after treatment compared to the pretreatment baseline. The latency to peak response to L-DOPA became shorter and reversed after the discontinuation of treatment. The duration of response showed minor changes. The pattern of changes in response to apomorphine was similar to that of L-DOPA except that the peak magnitude did not increase despite chronic L-DOPA treatment. The changes in D1 and D2 receptor binding did not correlate with behavioral changes. In summary, long-term intermittent L-DOPA treatment resulted in priming of antiparkinsonian effects on improving akinesia in a rat model of severe PD. These observed changes do not mirror all aspects of motor response fluctuations in advanced PD patients and suggest differential contributions of dopaminergic treatment and lesion severity to motor complication patterns.
[Show abstract][Hide abstract] ABSTRACT: Transforming growth factor-beta1 (TGF-beta1) promotes tissue fibrosis by upregulating genes encoding extracellular matrix proteins and by increasing the synthesis of plasminogen activator inhibitor-1 (PAI-1). TGF-beta1 induces cellular reactive oxygen species (ROS) and PAI-1 promoter region has binding sites for redox sensitive transcription factors. We, therefore, hypothesized that TGF-beta1-induced upregulation of PAI-1 is ROS-dependent. Using cultured glomerular mesangial cells, we confirmed that TGF-beta1 induces cellular ROS, upregulates PAI-1 mRNA and protein expression, and suppresses plasmin activity. We further demonstrated that H(2)O(2) stimulates PAI-1 expression and suppresses plasmin activity and that N-acetylcysteine effectively reverses TGF-beta1- and H(2)O(2)-induced changes in PAI-1 expression and plasmin activity. Basal as well as TGF-beta1- and H(2)O(2)-induced PAI-1 expression was upregulated by depletion of intracellular GSH. The present data demonstrate that TGF-beta1-induced PAI-1 in mesangial cells is ROS-dependent and imply that cellular ROS may be potential therapeutic targets in glomerular fibrosis.
Biochemical and Biophysical Research Communications 11/2003; 309(4):961-6. DOI:10.1016/j.bbrc.2003.08.102 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: By genetic analysis, the CAG repeat expansion has been established in spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7. Despite the genetic differentiation of SCA, the characterization of the phenotypes of various SCAs has been challenging for better clinical diagnosis.
To analyze the frequencies and the clinical manifestations of SCA1, SCA2, SCA3, SCA6, and SCA7 in Korean patients.
We performed genetic analysis in 253 unrelated Korean patients with progressive cerebellar ataxia. We compared the frequencies, inheritance patterns, and various clinical manifestations of patients with genetically confirmed SCA.
Among the 52 patients with expanded CAG repeat, the most frequent SCA type was SCA2, followed by SCA3, SCA6, SCA1, and SCA7. Nine patients (17%) had a negative family history of ataxia, mostly in SCA6. There were characteristic clinical features such as hypotonia and optic atrophy for SCA1; hyporeflexia for SCA2; nystagmus, bulging eye, and dystonia for SCA3; and macular degeneration for SCA7. Interestingly, 4 patients (1 with SCA2, 1 with SCA3, and 2 with SCA6) were misdiagnosed as having multiple-system atrophy because of the absence of family history and the presence of parkinsonism and urinary incontinence.
This study provides a detailed analysis of the clinical characteristics of the genetically defined CAG-repeat SCAs in Korean patients. Although phenotypes were heterogeneous, some clinical features may be helpful for clinical diagnosis. However, genetic studies for SCA are needed despite uncertain family history or the presence of atypical clinical features causing misdiagnosis as atypical parkinsonism.
[Show abstract][Hide abstract] ABSTRACT: The clonidine-growth hormone test (CGHT) has been proposed as a means of differentiating multiple system atrophy (MSA) from idiopathic Parkinson's disease (PD). However, it is controversial whether the CGHT is valid. We sought to confirm the validity of the CGHT and to compare the diagnostic accuracy of the CGHT with that of external anal sphincter electromyelography (Sph-EMG) for MSA. We performed the CGHT and the Sph-EMG on 21 PD patients, 23 patients with probable MSA of parkinsonian type (MSA-p), and 22 patients with probable MSA of cerebellar type (MSA-c). We compared the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of CGHT, Sph-EMG, and a combination of the two tests. We also evaluated the correlations of Unified Parkinson's Disease Rating Scale (UPDRS) scores with the results of the two tests. There was no significant difference between the UPDRS scores for the PD and MSA-p groups. Serum growth hormone concentrations after clonidine significantly increased in PD (mean increase +/- SEM, 4.19 +/- 0.92 ng/ml; P < 0.0001), but remained unchanged in both MSA-p (0.83 +/- 0.61 ng/ml) and MSA-c (1.45 +/- 0.58 ng/ml). The growth hormone responses to clonidine in MSA-p were significantly different from those in PD (P < 0.05). Abnormal, denervated Sph-EMG was observed in 95.7% of MSA-p, 86.4% of MSA-c, and 33.3% of PD patients. Compared to Sph-EMG, the CGHT was less sensitive but more specific in both MSA-p and MSA-c. The result of neither test correlated with the severity of parkinsonism. Interestingly, combining the results of the CGHT and Sph-EMG markedly increased the specificity (85.7% in the CGHT and 66.7% in Sph-EMG vs. 95.2% in the combination study) and the PPV in both MSA-p (85.7% and 75.9% vs. 94.4%) and MSA-c (82.4% and 73.1% vs. 91.7%). We confirm that the CGHT can distinguish MSA-p from PD. Its sensitivity is lower and its specificity higher than Sph-EMG. Compared to either test alone, combined testing with the CGHT and Sph-EMG increased specificity and PPV, thereby enhancing accuracy in the diagnosis of MSA.
Movement Disorders 11/2002; 17(6):1242-7. DOI:10.1002/mds.10225 · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Doxorubicin was chemically conjugated to the terminal end of a di-block copolymer composed of poly(L-lactic acid) (PLLA) and methoxy-poly(ethylene glycol) (mPEG) via two acid-cleavable linkages. A hydrazone bond and a cis-acotinyl bond were formed between doxorubicin and the terminal group of PLLA segment in the block copolymer. Doxorubicin-conjugated PLLA-mPEG di-block copolymers self-assembled to form micelles in aqueous solution. The doxorubicin-conjugated micelles were about 89.1 nm in diameter and their critical micelle concentration was 1.3 microg/ml. These values were comparable with those of unconjugated micelles. In an acidic condition, the conjugated doxorubicin in the hydrazone linkage was readily cleaved, releasing doxorubicin in an intact structure. Doxorubicin-conjugated PLLA-mPEG micelles were more potent in cell cytotoxicity than free doxorubicin, suggesting that they were more easily taken up within cells with concomitant rapid release of cleaved doxorubicin into the cytoplasm from acidic endosomes.
[Show abstract][Hide abstract] ABSTRACT: Enzymes have emerged as the most powerful alternatives to radioisotopes in the development of binding assay meth-ods for the selective detection of various physiological, bio-logical and environmental substances at trace levels. 1-6 Such methods may be classified as either heterogeneous (solid-phase) or homogeneous (separation-free). The heterogeneous arrangements such as the enzyme-linked immunosorbent assay (ELISA) are much slower, but prevalent. The homogeneous types such as the enzyme-multiplied immunoassay technique (EMIT) are much faster because there is no need for separa-tion of free and bound enzyme labels. 5,6 In this method, analytical signals result typically from inhibition of enzyme-conjugate catalytic activity in solution by antibody (or bind-ing protein) interactions with the conjugate. We have previously devised a generic type of the homo-geneous method based on the strong and specific biotin/avi-din interaction for the detection of biomolecules other than biotin. 7-10 In this method, the binding reaction between the enzyme-biotin and avidin-analyte conjugates inactivates the enzyme. In the presence of analyte-specific binder, the enzy-matic activity of the conjugate is regained (i.e., less inhib-ited) since the binding of the binder to the avidin-analyte conjugate prevents the enzyme inactivation by sterically hin-dering the binding between the avidin-analyte and enzyme-biotin conjugates. The biotin/avidin interaction may also be utilized in devising a heterogeneous assay protocol. For instance, the enzyme-biotin conjugate can serve as a signal generator by binding to the avidin-analyte conjugate that has already been bound to the analyte-specific binder immobi-lized on a solid surface. The aim of this work is to compare the analytical perfor-mance of several different enzyme-linked competitive bind-ing assay methods using a monoclonal anti-digoxin antibody as a model binder: i.e., homogeneous versus heterogeneous assays. and conventional EMIT or ELISA versus biotin/avi-din-mediated techniques. In this work, we further investi-gated the feasibility of developing an assay method useful for the determination of serum digoxin. Digoxin is the most widely used cardiac glycoside for treating congestive heart failure. 11,12 Because of a narrow therapeutic range (i.e., 0.8-2.0 ng/mL), serum digoxin levels are frequently determined throughout theraphy. 13 In this work, three different enzymes are examined as labels: i.e., glucose-6-phosphate dehydroge-nase (G6PDH), malate dehydrogenase (MDH), and alkaline phosphatase (ALP). Enzyme conjugates are evaluated in both heterogeneous and homogeneous assay protocols by com-paring the detection capabilities of the resulting assay sys-tems. The relative advantages and disadvantages of each assay protocol are discussed based upon the findings of this work.