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ABSTRACT: Chronic graft-versus-host disease (cGVHD) is a major complication in long-term survivors of hematopoietic stem cell transplantation (HSCT). Cutaneous manifestations are frequently the presenting features; therefore, the dermatologist needs to be aware of the wide spectrum of cutaneous cGVHD.
We retrospectively evaluated patients' characteristics, clinical, and histological features of cutaneous cGVHD and analyzed factors influencing the severity of cutaneous cGVHD in 100 Korean HSCT recipients between January 1, 1995, and December 31, 2007.
Clinical manifestations of cutaneous cGVHD mainly presented as lichenoid (60.0%), sclerodermoid (12.0%), or erythematous maculopapular (22.0%) patterns. Other less common findings included xerosis, dyspigmentation, acquired ichthyosis, eczema, exfoliative dermatitis, alopecia, erythema multiforme-like or keratosis pilaris-like eruption. Among 100 patients, 46 patients were investigated for nail involvement, and 29 (63.0%) of them were accompanied with nail abnormalities. Histologically, characteristic lichenoid lesions were observed in 53%, sclerodermoid in 9%, and acute/chronic overlap syndrome in 28% of patients. We also discovered that HSCT from female donors to male recipients increased the severity of cutaneous cGVHD.
We report a large study about cutaneous cGVHD in Asian patients. Cutaneous cGVHD presented with a wide spectrum of clinical and histological manifestations.
International journal of dermatology 12/2010; 49(12):1386-92. · 1.18 Impact Factor
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ABSTRACT: DDS, 4,4'-diaminodiphenylsulfone, is the most common drug prescribed to treat Hansen disease patients. In addition to its antibacterial activity, DDS has been reported to be involved in other cellular processes that occur in eukaryotic cells. Because DDS treatment significantly enhances the antioxidant activity in humans, we examined its effect on lifespan extension. Here we show that DDS extends organismic lifespan using Caenorhabditis elegans as a model system. DDS treatment caused a delay in aging and decreased the levels of a mitochondrial complex. The oxygen consumption rate was also significantly lowered. Consistent with these data, paraquat treatment evoked less reactive oxygen species in DDS-treated worms, and these worms were less sensitive to paraquat. Interestingly enough, all of the molecular events caused by DDS treatment were consistently reproduced in mice treated with DDS for 3 mo and in the C2C12 muscle cell line. Structural prediction identified pyruvate kinase (PK) as a protein target of DDS. Indeed, DDS bound and inhibited PK in vitro and inhibited it in vivo, and a PK mutation conferred extended lifespan of C. elegans. Supplement of pyruvate to the media protected C2C12 cells from apoptosis caused by paraquat. Our findings establish the significance of DDS in lowering reactive oxygen species generation and extending the lifespan, which renders the rationale to examining the possible effect of DDS on human lifespan extension.
Proceedings of the National Academy of Sciences 10/2010; 107(45):19326-31. · 9.68 Impact Factor
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ABSTRACT: Vitamin C is used as an anti-ageing agent because of its collagen enhancing effects. The precise cellular signalling mechanism of vitamin C is not well known. Here, we investigate the profibrotic mechanism of vitamin C against LL-37. Antimicrobial peptide LL-37 decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs). The ability of LL-37 to inhibit collagen expression is dependent on phosphorylation of extracellular signal-regulated kinase (ERK). HDFs and human keloid fibroblasts were treated with vitamin C followed by 2 h of LL-37 treatment. Collagen mRNA expression and total soluble collagen production inhibited by LL-37 was enhanced by treatment with 0.5 mm vitamin C. Vitamin C also decreased intracellular reactive oxygen intermediates (ROI) levels that were increased by LL-37. Furthermore, the phosphorylation of ERK was analysed by Western blot following treatment with vitamin C and LL-37. Vitamin C turned off phosphorylation of ERK that was induced by LL-37. Ets-1 transcriptional factor, which is involved in the regulation of collagen expression by LL-37, was also inhibited by vitamin C. This study shows that vitamin C enhances collagen production by inhibiting the ERK pathway induced by LL-37.
Experimental Dermatology 02/2010; 19(8):e258-64. · 3.54 Impact Factor
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ABSTRACT: Excessive accumulation of collagen contributes to the fibrotic process. Several experimental studies have shown that IFN-gamma is effective in preventing fibrogenesis. IL-18, originally identified as an IFN-gamma-inducing factor, is a key mediator of inflammation and host defense responses. In this study, we investigated the regulatory effect of IL-18 on the expression of type I and III collagen genes in dermal fibroblasts. The exposure of human dermal fibroblasts (HDFs) to IL-18 resulted in a reduction of collagen gene expression and production. Also, IL-18 inhibited the fibrogenic cytokine transforming growth factor (TGF)-beta-induced collagen gene expression. Next, to determine the molecular mechanism involved in this regulation, we showed that IL-18-regulated collagen expression was blocked by small interfering RNA (siRNA)-mediated Ets-1 knockdown. Furthermore, we showed that IL-18 induced phosphorylation of extracellular signal-regulated kinase (ERK) within 10 minutes and that the ERK inhibitor PD98059 blocked the inhibitory effect of IL-18. IL-18 also inhibited the production of collagen in systemic sclerosis (SSc) dermal fibroblasts. Our data indicate that IL-18 downregulates collagen production in HDF directly via Ets-1 and the ERK pathway, suggesting that IL-18 may exert antifibrotic activities in dermal fibroblasts.
Journal of Investigative Dermatology 10/2009; 130(3):706-15. · 6.31 Impact Factor
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ABSTRACT: Thermophilic biofiltration of H(2)S-containing gas was studied at 60 degrees C using polyurethane (PU) cubes and as a packing material and compost as a source of thermophilic microorganisms. The performance of biofilter was enhanced by pH control and addition of yeast extract (YE). With YE supplement and pH control, H(2)S removal efficiency remained above 95% up to an inlet concentration of 950 ppmv at a space velocity (SV) of 50h(-1) (residence time=1.2 min). H(2)S removal efficiency strongly correlated with the inverse of H(2)S inlet concentrations and gas flow rates. Thermophilic, sulfur-oxidizing bacteria, TSO3, were isolated from the biofilter and identified as Bacillus sp., which had high similarity value (99%) with Bacillus thermoleovorans. The isolate TSO3 was able to degrade H(2)S without a lag period at 60 degrees C in liquid cultures as well as in the biofilter. High H(2)S removal efficiencies were sustained with a periodic addition of YE. This study demonstrated that an application of thermophilic microorganism for a treatment of hot gases may be an economically attractive option since expensive pre-cooling of gases to accommodate mesophilic processes is not required.
Journal of hazardous materials 03/2009; 168(1):501-6. · 4.14 Impact Factor
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ABSTRACT: Tumor suppressor programmed cell death protein 4 (PDCD4) inhibits the translation initiation factor eIF4A, an RNA helicase that catalyzes the unwinding of secondary structure at the 5'-untranslated region of mRNAs and controls the initiation of translation. Here, we determined the crystal structure of the human eIF4A and PDCD4 complex. The structure reveals that one molecule of PDCD4 binds to the two eIF4A molecules through the two different binding modes. While the two MA3 domains of PDCD4 bind to one eIF4A molecule, the C-terminal MA3 domain alone of the same PDCD4 also interacts with another eIF4A molecule. The eIF4A-PDCD4 complex structure suggests that the MA3 domain(s) of PDCD4 binds perpendicular to the interface of the two domains of eIF4A, preventing the domain closure of eIF4A and blocking the binding of RNA to eIF4A, both of which are required events in the function of eIF4A helicase. The structure, together with biochemical analyses, reveals insights into the inhibition mechanism of eIF4A by PDCD4 and provides a framework for designing chemicals that target eIF4A.
Proceedings of the National Academy of Sciences 03/2009; 106(9):3148-53. · 9.68 Impact Factor
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IEICE Transactions. 01/2009; 92-B:2298-2302.
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ABSTRACT: The Mus81-Eme1 complex is a structure-specific endonuclease that plays an important role in rescuing stalled replication forks and resolving the meiotic recombination intermediates in eukaryotes. We have determined the crystal structure of the Mus81-Eme1 complex. Both Mus81 and Eme1 consist of a central nuclease domain, two repeats of the helix-hairpin-helix (HhH) motif at their C-terminal region, and a linker helix. While each domain structure resembles archaeal XPF homologs, the overall structure is significantly different from those due to the structure of a linker helix. We show that a flexible intradomain linker that formed with 36 residues in the nuclease domain of Eme1 is essential for the recognition of DNA. We identified several basic residues lining the outer surface of the active site cleft of Mus81 that are involved in the interaction with a flexible arm of a nicked Holliday junction (HJ). These interactions might contribute to the optimal positioning of the opposite junction across the nick into the catalytic site, which provided the basis for the "nick and counternick" mechanism of Mus81-Eme1 and for the nicked HJ to be the favored in vitro substrate of this enzyme.
Genes & Development 05/2008; 22(8):1093-106. · 11.66 Impact Factor
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ABSTRACT: The GINS complex mediates the assembly of the MCM2-7 (minichromosome maintenance) complex with proteins in a replisome progression complex. The eukaryotic GINS complex is composed of Sld5, Psf1, Psf2, and Psf3, which must be assembled for cell proliferation. We determined the crystal structure of the human GINS complex: GINS forms an elliptical shape with a small central channel. The structures of Sld5 and Psf2 resemble those of Psf1 and Psf3, respectively. In addition, the N-terminal and C-terminal domains of Sld5/Psf1 are permuted in Psf2/Psf3, which suggests that the four proteins have evolved from a common ancestor. Using a structure-based mutational analysis, we identified the functionally critical surface regions of the GINS complex.
Genes & Development 07/2007; 21(11):1316-21. · 11.66 Impact Factor
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ABSTRACT: Sounding provides a BS with knowledge of the channel state information of a user in an orthogonal frequency division multiple access (OFDMA) full duplex division (FDD) uplink. In this paper, we propose a novel sounding subband allocation algorithm for the proportional fair (PF) scheduler. Simulation results show that our proposed sounding method enables the PF scheduler to achieve the throughput gain and guarantee fairness at the same time.
Vehicular Technology Conference, 2007. VTC2007-Spring. IEEE 65th; 05/2007
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ABSTRACT: Werner syndrome is a premature aging disease caused by mutations in the WS gene and a deficiency in the function of Werner protein (WRN). The lack of WRN results in a cellular phenotype of genomic instability. WRN belongs to the RecQ DNA helicase family, but unlike other RecQ family members it possesses a functional exonuclease domain. We determined the crystal structure of mWRNexo (residues 31-238) bound to Zn(2+) and the sulfate ion. Compared with the structure of human WRNexo (hWRNexo), notable conformational changes were observed in several active site residues in an H5-H6 loop and in helices H6 and H7 of mWRNexo, presumably because of the presence of sulfate, which mimics the phosphate of substrate DNA. In particular, the side chains of Lys(185) and Tyr(206) were reoriented toward the Zn(2+) ion, whereas the side chain of Arg(190) pointed away from the active site center. Mutational analysis of these conserved residues abolished WRN exonuclease activity, suggesting that these residues play a critical role in the WRNexo activity. Based on substrate modeling and mutational analyses, we propose a mechanism by which WRNexo becomes activated upon substrate DNA binding. We also describe the low resolution trimeric structure of mouse WRNexoL (mWRNexoL, residues 31-330), as elucidated by small angle x-ray scattering (SAXS) analyses.
Journal of Biological Chemistry 04/2007; 282(13):9941-51. · 4.77 Impact Factor
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ABSTRACT: An initial timing offset estimation method for orthogonal frequency-division multiplexing (OFDM) systems is proposed. Conventional preamble-based synchronization methods result in performance degradation due to the time variation in the power delay profile of the channel. We propose a simple but efficient synchronization method using a specifically designed preamble. The performance of the proposed estimator is evaluated by computer simulations. The simulation results show that the proposed estimator has a significantly smaller mean squared error (MSE) than other estimators even in the fast varying channel.
Vehicular Technology Conference, 2006. VTC-2006 Fall. 2006 IEEE 64th; 10/2006
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ABSTRACT: In the interleaved orthogonal frequency-division multiple access (OFDMA) uplink, the received signal from a user is corrupted by the intercarrier interferences (ICI) which result from both his own signal and other users' signals due to Doppler spreads. Furthermore, different received signal powers and Doppler spreads between users may increase the effect of the ICI. Among the schemes which have been proposed to reduce the ICI in OFDM, the ICI self-canceling scheme is easily applicable to the interleaved OFDMA uplink. In this paper, we investigate the performance of the interleaved OFDMA uplink with and without ICI self-canceling over doubly dispersive channels. We analyzed the signal-to-intercarrier-interference-plus-noise ratio (SINR) improvement and we examined the symbol error rates and the error floors through simulation.
Vehicular Technology Conference, 2006. VTC-2006 Fall. 2006 IEEE 64th; 10/2006
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ABSTRACT: In eukaryotes, misfolded proteins must be distinguished from correctly folded proteins during folding and transport processes by quality control systems. Yeast peptide:N-glycanase (yPNGase) specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists proteasome-mediated glycoprotein degradation by forming a complex with 26S proteasome through DNA repair protein, yRad23. Here, we describe the crystal structures of a yPNGase and XPC-binding domain of yRad23 (yRad23XBD, residues 238-309) complex and of a yPNGase-yRad23XBD complex bound to a caspase inhibitor, Z-VAD-fmk. yPNGase is formed with three domains, a core domain containing a Cys-His-Asp triad, a Zn-binding domain, and a Rad23-binding domain. Both N- and C-terminal helices of yPNGase interact with yRad23 through extensive hydrophobic interactions. The active site of yPNGase is located in a deep cleft that is formed with residues conserved in all PNGase members, and three sugar molecules are bound to this cleft. Complex structures in conjunction with mutational analyses revealed that the walls of the cleft block access to the active site of yPNGase by native glycoprotein, whereas the cleft is sufficiently wide to accommodate denatured glycoprotein, thus explaining the specificity of PNGase for denatured substrates.
Proceedings of the National Academy of Sciences 07/2005; 102(26):9144-9. · 9.68 Impact Factor
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ABSTRACT: To maintain chromosome stability in eukaryotic cells, replication origins must be licensed by loading mini-chromosome maintenance (MCM2-7) complexes once and only once per cell cycle. This licensing control is achieved through the activities of geminin and cyclin-dependent kinases. Geminin binds tightly to Cdt1, an essential component of the replication licensing system, and prevents the inappropriate reinitiation of replication on an already fired origin. The inhibitory effect of geminin is thought to prevent the interaction between Cdt1 and the MCM helicase. Here we describe the crystal structure of the mouse geminin-Cdt1 complex using tGeminin (residues 79-157, truncated geminin) and tCdt1 (residues 172-368, truncated Cdt1). The amino-terminal region of a coiled-coil dimer of tGeminin interacts with both N-terminal and carboxy-terminal parts of tCdt1. The primary interface relies on the steric complementarity between the tGeminin dimer and the hydrophobic face of the two short N-terminal helices of tCdt1 and, in particular, Pro 181, Ala 182, Tyr 183, Phe 186 and Leu 189. The crystal structure, in conjunction with our biochemical data, indicates that the N-terminal region of tGeminin might be required to anchor tCdt1, and the C-terminal region of tGeminin prevents access of the MCM complex to tCdt1 through steric hindrance.
Nature 09/2004; 430(7002):913-7. · 36.28 Impact Factor
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ABSTRACT: We investigate an adaptive subcarrier, bit, and power allocation algorithm for the downlink MIMO-OFDMA system. Using the singular value decomposition, the MIMO fading channel of each subcarrier is transformed into an equivalent bank of parallel SISO sub-channels. For the efficient allocation of the banks of parallel sub-channels, we define the problem of minimizing total transmit power with constraints on BER and transmission rate for users. Using the simplified problem formulation, we propose a sub-optimal adaptive subcarrier, bit, and power allocation algorithm which outperforms the fixed subcarrier allocation in the MIMO-OFDMA system.
Vehicular Technology Conference, 2004. VTC 2004-Spring. 2004 IEEE 59th; 06/2004
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ABSTRACT: This paper investigates the adaptive subcarrier and bit allocation algorithm for OFDMA systems. To minimize overall transmit power, we propose a novel adaptive subcarrier and bit allocation algorithm based on channel state information, Moreover, the block-wise method is considered based on channel variation for adaptive subcarrier and bit allocation. It is shown that a near optimal solution is obtained by the proposed algorithm which has low complexity compared to that of other conventional algorithms. Also, it is shown that the block-wise method significantly reduces the complexity and the feedback or side information though has a slight transmit power increase.
Vehicular Technology Conference, 2004. VTC 2004-Spring. 2004 IEEE 59th; 06/2004
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ABSTRACT: RNase PH is a phosphate-dependent exoribonuclease that catalyzes the removal of nucleotides at the 3' end of the tRNA precursor, leading to the release of nucleoside diphosphate, and generates the CCA end during the maturation process. The 1.9-A crystal structures of the apo and the phosphate-bound forms of RNase PH from Pseudomonas aeruginosa reveal a monomeric RNase PH with an alpha/beta-fold tightly associated into a hexameric ring structure in the form of a trimer of dimers. A five ion pair network, Glu-63-Arg-74-Asp-116-Arg-77-Asp-118 and an ion-pair Glu-26-Arg-69 that are positioned symmetrically in the trimerization interface play critical roles in the formation of a hexameric ring. Single or double mutations of Arg-69, Arg-74, or Arg-77 in these ion pairs leads to the dissociation of the RNase PH hexamer into dimers without perturbing the overall monomeric structure. The dissociated RNase PH dimer completely lost its binding affinity and catalytic activity against a precursor tRNA. Our structural and mutational analyses of RNase PH demonstrate that the hexameric ring formation is a critical feature for the function of members of the RNase PH family.
Journal of Biological Chemistry 02/2004; 279(1):755-64. · 4.77 Impact Factor
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ABSTRACT: Degradation characteristics of toluene in enrichment culture were investigated in soil microcosms study and the optimum environmental conditions for anaerobic degradation of toluene coupled with sulfate reduction were determined for field site applications. Anaerobic sulfate-reducing bacteria were enriched from oil contaminated soil samples with toluene. Enriched consortia degraded toluene with sulfate as a terminal electron acceptor. The average degradation rate of toluene in enriched consortia ranged from 0.08 to 0.1 micromol g(-1) day(-1). Toluene degradation under sulfate-reducing condition was inhibited in the presence of molybdate alone or together with nitrate or fumarate, indicating that toluene is degraded directly by sulfate-reducing bacteria. Effects of initial toluene concentration, pH, temperature, and other hydrocarbons on toluene degradation were investigated. There is a trend of increasing rate of toluene degradation with increasing the initial mass up to 94 micromol of toluene. Toluene degradation did not affected by the presence of ethylbenzene and xylene, as a while, toluene was degraded in a slower rate in the presence of benzene. The sulfate-reducing bacteria in the enriched culture showed higher microbial activity at neutral (pH 6-8) and medium temperature (30-37 degrees C) environments.
Journal of Environmental Science and Health Part A 07/2003; 38(6):1087-97. · 1.19 Impact Factor
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ABSTRACT: This paper proposes an adaptive tap allocation technique based on the Kalman algorithm for minimizing the number of taps which are used for updating the equalizer coefficient. The conventional equalizer needs many taps to be adequate for the multipath channel with a long delay, which causes a high computational complexity for updating the coefficient. We propose a new method that the energy of tap and the channel delay length are observed during a training period and then the taps having negligible energy are gradually excluded from the coefficient update every channel delay length. The remaining taps form a new coefficient vector that reduces the computational complexity without any performance degradation. The proposed structure is simulated on the channel of the North American terrestrial high definition television (HDTV). Simulation results show that the computational complexity is almost 25 times lower than that of the conventional structure with the same convergence speed and mean square error (MSE) rate.
Communication Systems, 2002. ICCS 2002. The 8th International Conference on; 12/2002
