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Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) plaques and neurofibrillary tangles. AD drug development has been limited due to the presence of the blood–brain barrier (BBB), which prevents efficient uptake of therapeutics into the brain. To solve this problem, we used trans-activator of transcription (TAT)-transducing domain and added the human serum albumin (HSA) carrier to increase the half-life of the drug within the body. In addition, we included the protein of interest for lowering Aβ deposition and/or neurofibrillary tangles. We made HSA fusion protein (designated AL04) which contains Cystatin C (CysC) as core mechanism of action moiety in the construct containing tandem repeat TAT (dTAT). After purification of 80KDa AL04, we investigate the therapeutic potential of AL04 in vitro and AD mouse model Tg2576. We evaluated the permeability of AL04 through the BBB using a cell-based human BBB model and show that dTAT plays a role in facilitating the delivery of 80 kDa protein. We found out that AL04 attenuates Aβ-induced neurotoxicity in PC12 cells. In Tg2576 mice brain, Aβ plaques were dramatically reduced in AL04 treated mice. These data suggest that BBB-crossing albumin fusion protein AL04 with CysC active moiety can be a disease modifying treatment for AD.

This paper presents the results of a case study on a wind characteristic analysis performed using a probabilistic distribution function to evaluate the meteorology of the Kori and Wolsong nuclear power plants (NPPs) in the Republic of Korea. The return period for daily extreme wind speed considering the wind direction was estimated using a Weibull distribution for the Kori and Wolsong NPP sites. From the directional wind calculation, the Weibull scale parameter c ranged from 5.83 to 9.06 at the Kori site and from 4.53 to 6.79 at the Wolsong site. The shape parameter k ranged from 1.97 to 3.59 at the Kori site and from 2.56 to 4.77 at the Wolsong site. The minimum and maximum directional wind speeds for the return period were 10.29 and 21.00 m/s in the WSW and WNW directions, respectively, at the Kori site and 6.54 and 12.07 m/s, respectively, at the Wolsong site. The results of this research offer a useful reference to evaluate the site safety assessment for the construction of Shin-Kori units 5 and 6 near the Kori site and a 2nd-stage low-intermediate level radioactive waste depository site near the Wolsong site. The study results can also be utilized to plan an evacuation pathway during unexpected radiation emergency conditions.

Two radionuclides ( 131 I and 137 Cs) were measured and simulated over the Korean Peninsula during the Fukushima Dai-ichi nuclear accident, and the resulting meso-scale meteorological characteristics were explored in order to interpret the medium-range transport of radionuclides from the site of the Fukushima Dai-ichi nuclear accident to the Korean Peninsula. Peak concentrations of radionuclides were detected across all sites in Korea for a period of April 2–8, 2011, with maximum concentrations of 131 I and 137 Cs at 3.12 mBq/m 3 (on April 6), and 1.25 mBq/m 3 (on April 7), respectively; the highest levels on record in Korea since measurements began. The multi-particle Lagrangian model, the FLEXPART simulation based on the National Centers for Environmental Prediction/Global Forecast System (NCEP/GFS), successfully explored these high radionuclide peaks resulting from long- and medium-range transport processes from the accident site. The meteorological feature of the medium-range transport exploited in this study is the veering meso-scale circulation, in association with the presence of a blocking anticyclone, and its subsequent evolution with propagation eastwards over northeast Asia, which was one of the important factors in explaining the advection and redirection of radionuclides from the accident site to the Korean Peninsula. The blocking situation of the anticyclone, centered on the Korean Peninsula, lasted for two days (on April 4–5, 2011), and the northwesterlies and subsequent northerlies advected the radionuclides from the accident site to the southern Sea of Japan. They were then redirected towards Korea due to the veering circulations produced by the blocking anticyclone. The position-evolution of the anticyclone was concurrent with the timing of the transport of the highest level of 137 Cs concentrations recorded in Korea. The vertical meteorological structure of the blocking anticyclone was also well featured to maintain its position due to the persistent compensation provided by being aloft a convergence zone, which is in good accordance with the location of the ridge on the 500 hPa level.

This study conducted shear strength test and plate bearing test to look into the characteristics of bearing capacity using geosynthetics case on forest road surface. The shear strength test showed that the internal friction angle at the time when geosynthetics was used was measured larger on average than that in the unreinforced case. Therefore, using geosynthetics case produced more bearing capacity reinforcement effect. The result from the comparison test of internal friction angle by geosynthetics type revealed that the internal friction angle at the time when geotextile case was used was measured larger. That was attributable to the difference between the area of the total cross section of geotextile made in type of non-woven fabric and its material. Plate bearing test showed that the settlement at the time when geosynthetics was used was measured smaller than that in the unreinforced case. Therefore, using geosynthetics produced more bearing power reinforcement effect. The result from the comparison test showed that geogrid case was measured smaller than geotextile case. Henceforth, It is seemed that it will be necessary to keep studying the reinforcement engineering and process of forest road surface which fits the characteristics and conditions of geosynthetics to prevent forest road demage.

The effects of a dietary probiotic mixture containing Lactococcus (Lc.) lactis BFE920 isolated from bean sprout and autochthonous Lactobacillus (Lb.) plantarum FGL0001 originally isolated from the hindgut of olive flounder (Paralichthys olivaceus) were investigated for the purpose of improving the probiotic effects of Lc. lactis BFE920 on the olive flounder. The immunostimulatory, disease protective, and weight gain effects of Lc. lactis BFE920 were significantly improved when olive flounder (average weight 37.5±1.26 g) were fed the probiotic mixture (log10 7.0 CFU each/g feed pellet) for 30 days. Flounder fed the mixture showed improved skin mucus lysozyme activity and phagocytic activity of innate immune cells compared to flounder fed a single probiotic agent or a control diet. While the levels of neutrophil activity in flounder fed the single probiotic agent or the mixture were similar, they were significantly higher than levels in a control group. Additionally, probiotic-fed flounder showed significantly increased expressions of IL-6, IL-8, and TNF-α in the intestine compared to the control group. Following a 30-day period of being fed probiotics or a control diet, the olive flounder were challenged with an i.p. injection of Streptococcus iniae (log10 6.0 CFU/fish). The groups fed the mixed probiotics, Lc. lactis BFE920, Lb. plantarum FGL0001, and the control diet had survival rates of 55%, 45%, 35%, and 20%, respectively. Flounder fed the probiotic mixture gained 38.1±2.8% more body weight compared to flounder fed the control diet during the 30-day study period. These data strongly suggest that a mixture of Lc. lactis BFE920 and Lb. plantarum FGL0001 may serve as an immunostimulating feed additive useful for disease protection in the fish farming industry.

Edwardsiellosis is a major fish disease that causes a significant economic damage in the aquaculture industry. Here, we assessed vaccine efficacy after feeding oral vaccines to olive flounder (Paralichthys olivaceus), either L. lactis BFE920 expressing Edwardsiella tarda outer membrane protein A (OmpA), flagellar hook protein D (FlgD), or a fusion antigen of the two. Feed vaccination was done twice with a one-week interval. Fish were fed regular feed adsorbed with the vaccines. Feed vaccination was given over the course of one week to maximize the interaction between the feed vaccines and the fish intestine. Flounder fed the vaccine containing the fusion antigen had significantly elevated levels T cell genes (CD4-1, CD4-2, and CD8α), type 1 helper T cell (Th1) subset indicator genes (T-bet and IFN-γ), and antigen-specific antibodies compared to the groups fed the single antigen-expressing vaccines. Furthermore, the superiority of the fusion vaccine was also observed in survival rates when fish were challenged with E. tarda: OmpA-FlgD-expressing vaccine (82.5% survival); FlgD-vaccine (55.0%); OmpA-vaccine (50%); WT L. lactis BFE920 (37.5%); Ctrl (10%). In addition, vaccine-fed fish exhibited increased weight gain (∼20%) and a decreased feed conversion ratio (∼20%) during the four week vaccination period. Flounder fed the FlgD-expressing vaccine, either the single or the fusion form, had significantly increased expression of TLR5M, IL-1β, and IL-12p40, suggesting that the FlgD may be a ligand of olive flounder TLR5M receptor or closely related to the TLR5M pathway. In conclusion, the present study demonstrated that olive flounder fed L. lactis BFE920 expressing a fusion antigen composed of E. tarda OmpA and FlgD showed a strong protective effect against edwardsiellosis indicating this may be developed as an E. tarda feed vaccine.

The synthesis of Si nanoparticles by ultrasonication processing of porous Si powder and a novel method for preparing a high-capacity Si/C composite using this technique is reported. The porous Si powder is prepared by selectively etching the silicide phase of a Ti 24 Si 76 alloy consisting of Si and silicide phases. The particle size of the nanocrystalline Si is determined by the crystallite size of the Si and silicide phases in the alloy powder. Ultrasonication of the porous Si obtained from the mechanically alloyed Ti 24 Si 76 alloy generates nanocrystalline Si particles of size about 5 nm. Growth of the Si and silicide phases in the alloy is induced by annealing of the mechanically alloyed sample, with a consequent increase in the size of the Si particles obtained after ultrasonication. Application of the ultrasonication process to the fabrication of Si/C composite anode materials generates nanometer-scale Si particles in situ that are distributed in the matrix. Analysis of the phases obtained and evaluation of the distribution of the nanometer-scale Si particles in the composites via XRD/TEM measurements show that the nanometer-scale Si particles are effectively synthesized and uniformly distributed in the carbon matrix, leading to enhanced electrochemical performance of the Si/C composites.

In this study, we found that BMP2 exerts neurotrophic effects, including a neuroprotective effect against nocodazole-induced neuritic degeneration, on neuronal cells. We also found that BMP2-induced neurotrophic effects are directly involved in Smad-dependent signaling as well as PI3K/PTEN-Akt-mTOR signaling. Moreover, BMP2-induced neurotrophic effects occur by stabilization of neuronal microtubules. Thus, these findings suggest that BMP2 can be a potential therapeutic target for nerve injury treatment.

Objectives Nicotine is a natural alkaloid and insecticide in tobacco leaves. Green tobacco sickness (GTS) is known as a disease of acute nicotine intoxication among tobacco farmers. Until now, GTS has been recognized globally as a disease that results from nicotine absorption through the skin. However, we assumed that GTS might also result from nicotine inhalation as well as absorption. We aimed to measure the airborne nicotine concentrations in various work environments of Korean tobacco farmers. Methods We measured the nicotine concentrations in the tobacco fields, private curing barns, and joint curing barns of farmers from July to October 2010. All sampling and analyses of airborne nicotine were conducted according to the National Institute for Occupational Safety and Health manual of analytic methods. Results The airborne nicotine concentrations (geometric mean [geometric standard deviation]) in the tobacco field were 83.4 mg/m(3) (1.2) in the upper region and 93.3 mg/m(3) (1.2) in the lower region. In addition, the nicotine concentration by personal sampling was 150.1 mg/m(3). Similarly, the nicotine concentrations in the private curing barn, workers in curing barns, the front yard of the curing barn, and in the joint curing barn were 323.7 mg/m(3) (2.0), 121.0 mg/m(3) (1.5), 73.7 mg/m(3) (1.7), and 610.3 mg/m(3) (1.0), respectively. Conclusions The nicotine concentration in the workplaces of tobacco farmers was very high. Future studies should measure the environmental concentration of nicotine that is inhaled by tobacco farmers.

We demonstrate the possibility of controlling organic light-emitting diodes (OLEDs) efficiency with an optimized hole-delay layer (HDL) in order to achieve very high contrast ratio needed for active matrix display applications. No triplet exciton confinement structure and a molybdenum trioxide (MoO 3 ) HDL at ITO/hole transport layer interface were used for a careful placing and adjusting of the exciton recombination zone. An optimized thickness of 50 nm thick MoO 3 allows to cut off the efficiency at the black level of active matrix driving mode while it gets greater at higher luminance at high current density region over 20 mA/cm 2 compared to conventional device. Our suggested efficiency control way is believed to be very useful to future active matrix OLED displays.

The protective effect of a food-grade lactic acid bacterium Lactococcus lactis BFE920 against disease of olive flounder (Paralichthys olivaceus) cultivated on a large scale was studied. Initially, antimicrobial activity of L. lactis against several fish pathogens was evaluated in vitro; the probiotic showed strong antibacterial activity against Streptococcus iniae, Streptococcus parauberis and Enterococcus viikkiensis, and moderate activity against Lactococcus garviae. When olive flounders were fed for two weeks with experimental diets containing varying concentrations of L. lactis (1 × 10(6), 5 × 10(6), 2.5 × 10(7) and 1.25 × 10(8) CFU/g feed), all the experimental feed groups showed 68-77% survival upon challenge with S. iniae. A field-scale feeding trial with L. lactis dietary supplement was conducted in a local fish farm (n = 12,000) for three months, and disease resistance, innate immune parameters and growth performance were evaluated. The average weight gain and feed efficiency were increased up to 6.8% and 8.5%, respectively. At the end of the feeding trial, the olive flounders were challenged with S. iniae. The L. lactis-fed group was protected from S. iniae challenge with a 66% survival rate. This disease protection is due to the flounder's innate immunity activated by the L. lactis administration: increased lysosomal activities and production of IL-12 and IFN-γ. These data clearly indicated that L. lactis BFE920 may be developed as a functional feed additive for protection against diseases, and for enhancement of feed efficiency and weight gain in olive flounder farming.

A Memristor theorized by Chua in 1971 has the potential to dramatically influence the way electronic circuits are designed. It is a two terminal device whose resistance state is based on the history of charge flow brought about as the result of the voltage being applied across its terminals and hence can be thought of as a special case of a reconfigurable resistor. Nanoscale devices using dense and regular fabrics such as Memristor cross-bar is promising new architecture for System-on-Chip (SoC) implementations in terms of not only the integration density that the technology can offer but also both improved performance and reduced power dissipation. Memristor has the capacity to switch between high and low resistance states in a cross-bar circuit configuration. The cross-bars are formed from an array of vertical conductive nano-wires cross a second array of horizontal conductive wires. Memristors are realized at the intersection of the two wires in the array through appropriate processing technology such that any particular wire in the vertical array can be connected to a wire in the horizontal array by switching the resistance of a particular intersection to a low state while other cross-points remain in a high resistance state. However the approach introduces a number of challenges. The lack of voltage gain prevents logic being cascaded and voltage level degradation affects robustness of the operation. Moreover the cross-bars introduce sneak current paths when two or more cross points are connected through the switched Memristor. In this paper, we propose Memristor-based programmable logic array (PLA) architecture and develop an analytical model to analyze the logic level on the memristive networks. The proposed PLA architecture has 12 inputs maximum and can be cascaded for more input variables with R(off)/R(on) ratio in the range from 55 to 160 of Memristors.

This study is performed to light up the semiotic system of streetscape in the harbor on the basic concept of all cultural phenomena that could be described as a Semiotic System. The semiotic approach to landscape analysis was used for understanding landscape characteristics owing to implication of psychological process. Streets of the study were located at Ganguri and Opori on Gang-Gu Harbor and the signboard semiotics of streets were divided into 17 meanings according to the business category. The analysis of this category was applicable on semiotic meaning. The research results are as follows: First, the main part of the business category was food. 56.3% of Ganguri and 61.8% of Opori had the name of food businesses. Second, the semiotic characteristics of Gang-Gu harbor streets mainly mean place name or friendly name. The food business could be related to the principal products of this district which are called Young-Duk Great Crab. Also, the place name could be from symbolic meaning of the crab and the friendly name could be connected with increasing the sales. Finally, the semiotic approach to landscape does not fully cover the streetscape but could be useful for understanding a skeleton of harbor streetscape.

The standard unit manpower and material in landscape architectural construction was consist of a standard and universal work classification. However, these constructional methods have created a number of problems in utilizing and responding on a variety of recently-developed working methods such as new constructional skills and technologies. This research decided that presenting the amendments of work classification of a standard unit manpower and material in landscape architectural construction was very important, and investigated those work classifications which required these new amendments. First of all, assessment items were selected through the literature reviews and a preliminary survey. Then, these assessment items were surveyed to the total of 60 professional landscape architecture field. The results of this study were as follows; First, the utilization level of the a standard unit manpower and material in landscape architectural construction was highest in the area of work classification of planting unit manpower and material. Second, the work classifications that needed to be added were recognized as leveling the ground construction, landscape structure construction, paving construction, water facilities construction, and outdoor facilities construction. Third, in the field of the a standard unit manpower and material in landscape architectural construction, 66.7% of the respondents replied that some amendments were necessary, and those amendments needed work classifications were identified as work classification of planting unit manpower and material was gigantic plant, topiary tree, temporary planting, exchange dead tree, etc. In the area of digging out was gigantic plant and plastic tree were recognized. The survey respondents also answered that, in keeping and management work classifications some amendments in pruning waste were necessary, and in the fields of rubble masonry work classifications some improvements were required in rubble aperture planting unit manpower and material and sodding and herbaceous sowing was a realistic lawn size unit manpower and material was needed. Based on the results explained above, this study suggests that amendments for a standard unit manpower and material in landscape architectural construction are necessary, especially in the areas of planting size and quality of work classifications unit manpower and material and in the unit manpower and material that affects the quality of lands caping constructions.

There have been major changes since the incidents of leukemia development in X-SCID patients after the treatments using retroviral gene therapy. Due to the risk of oncogenesis caused by retroviral insertional activation of host genes, most of the efforts focused on the lentiviral therapies. However, a relative clonal dominance was detected in a patient with β-thalassemia Major, two years after the subject received genetically modified hematopoietic stem cells using lentiviral vectors. This disappointing result of the recent clinical trial using lentiviral vector tells us that the current and most advanced vector systems does not have enough safety. In this review, various safety features that have been tried for the retroviral gene therapy are introduced and the possible new ways of improvements are discussed. Additional feature of chromatin insulators, co-transduction of a suicidal gene under the control of an inducible promoter, conditional expression of the transgene only in appropriate target cells, targeted transduction, cell type-specific expression, targeted local administration, splitting of the viral genome, and site specific insertion of retroviral vector are discussed here.

Purpose: Our goal of this study was to compare the mechanism of injury and the clinical outcomes between the non-traumatic and traumatic type II SLAP lesions. Materials and Methods: From January 2007 to May 2009, the sunjects of this study were 27 patients who had undergone operations for isolated type II SLAP lesions. The lesions were classified according to Burkhart’s method. The lesions that were located on the anterior-superior labrum were classified as type I, those lesions located on the posterior-superior labrum were classified as type II and those lesions located on the anterior-posterior labrum were classified as type III. The clinical outcomes were evaluated by the UCLA score and the KSS score preoperatively and postoperatively. Results: Of the 27 cases, 16 cases were traumatic and eleven cases were non-traumatic. In the traumatic group, there were 12, 2 and 2 cases of type I, type II and type III, respectively (p=0.013). In non-traumatic group, there were 2, 6 and 3 cases of type I, type II and type III (p=0.026). Anterior lesions were more frequent in the traumatic group and posterior lesions were more frequent in the non-traumatic group. For the clinical outcomes, the mean preoperative UCLA score and KSS score were 18 (range: 14~23) and 48 (range: 32~76), respectively, and the postoperative UCLA score and KSS score were 32 (range: 28~33) and 86 (range: 71~92), respectively, in the traumatic group, and the preoperative UCLA score and KSS score were 21 (18~25) and 58 (41~68), respectively, and the postoperative UCLA score and KSS score were 29 (26~31) and 81 (68~89), respectively in the non-traumatic group. There was no significant statistical difference of clinical outcomes between the two groups (p=0.317, 0.405). Conclusion: In this study, the anatomical feature of type II SLAP lesion was associated with a trauma mechanism. Therefore, a trauma mechanism must be considered when planning the surgical treatment for type II SLAP lesions.

Korean mistletoe lectin (KML-C) is an adjuvant that activates systemic and mucosal immune cells to release cytokines including TNF-alpha, which induces immunity against viruses and cancer cells. Although the immunomodulatory activity of KML-C has been well established, the underlying mechanism of action of KML-C has yet to be explored. When mouse peritoneal macrophages were treated with KML-C, both transcription and translation of TLR4 were upregulated. KML-C-induced TLR4 downstream events were similar to those activated by LPS: the upregulation of interleukin-1 receptor-associated kinase-1 (IRAK1); resulting in macrophage activation and TNF-alpha production. When TLR4 was blocked using a TLR4-specific neutralizing antibody, TNF-alpha production from the macrophages was significantly inhibited. Moreover, TLR4-deficient mouse macrophages treated with KML-C also secreted greatly reduced level of TNF-alpha secretion. Finally, TLR4 molecules were co-precipitated with KML-C, to which agarose beads were conjugated, indicating that those molecules are associated. These data indicate that KML-C activates mouse macrophages to secrete TNF-alpha by interacting with the TLR4 molecule and activating its signaling pathways.

This work has investigated filling characteristics during injection molding of a thin-plate with microchannel patterns on it. To conduct molding experiments, an injection mold and mold inserts with microchannel patterns were designed and built. The experiments were conducted for three different channel sizes, and the results are analyzed. An unstable filling flow was observed in microscopic images for the smallest channel size. The front advanced with continuous creation and merge of microballs, which looked like teeth on the gum. We have analyzed this phenomenon and argued that there exists a critical channel width where such instability takes places. POLYM. ENG. SCI., 50 :137 7 -1381, 2010. © 2010 Society of Plastics Engineers.

Background aims The aim was to evaluate cartilage regeneration in animal models involving induced knee joint damage. Through cell-mediated gene therapy methods, a cell mixture comprising a 3:1 ratio of genetically unmodified human chondrocytes and transforming growth factor beta-1 (TGF-β1)-secreting human chondrocytes (TG-C), generated via retroviral transduction, resulted in successful cartilage proliferation in damaged regions. Methods Non-clinical toxicology assessments for efficacy, biodistribution and local/systemic toxicity of single intra-articular administration of the cell mixture in mice, rabbits and goats was conducted. Results Administration of the mixture was tolerated well in all of the species. There was evidence of cartilage proliferation in rabbits and goats. As an additional precautionary step, the efficacy of TGF-β1 secretion in irradiated human chondrocytes was also demonstrated. Conclusions Four studies in rabbits and goats demonstrated the safety and efficacy of TG-C following direct intra-articular administration in animal models involving induced knee joint damage. Based on these pre-clinical studies authorization has been received from the USA Food and Drug Administration (FDA) to proceed with an initial phase I clinical study of TG-C for degenerative arthritis.

19세여자환자는수상당일단체줄넘기시합에서줄을넘기는역할을하던중줄이사람에걸리면서우측팔이급격히당겨지며앞으로넘어지면서유발된우측견관절통증을주소로내원하였다. 처음내원시우측견관절통증은VAS 점수9점으로극심한통증을호소하였다. 통증이심하여견관절이학적검사는시행하지못하였다.단순방사선검사에서이상소견은관찰되지않았다.따라서어깨관절고정보조기를착용하여1주일간의경과관찰을시행하였다. 1주후내원시어깨관절통증은VAS 점수7점으로통증은 감소하였으나, 여전히견관절운동시심한통증을호소하였다. 어깨관절운동은전범위가가능하여이학적검사를시행하였다. 이학적검사상상완이두근장두검사에서 Speed 검사양성소견및Yergason 검사음성소견을 보였다.또한SLAP 병변에대한이학적검사상, O’Brien 검사양성소견, Compression-Rotation 검사양성소견을보였다. Sulcus 검사및Kim’s 검사등은음성소견을보였으며, 전방불안정성및후방불안정성은관찰되지않았다. UCLA 견관절점수는18점으로불량하였다. 정밀검사를위하여자기공명관절조영술을시행하였다. 경사관상면(Oblique coronal view)에서, 조영제에의해상완이두근장두부착부위가상부관절와순으로부터분리되어지는소견을보였다. 관절순하공과구별이쉽지않았으나, 조영제에의한분리면이불규칙하여단계2 SLAP병변이더의심되었다. 축상면(Axial view)에서전방및후방의관절낭파열및분리소견은보이지않았으나, 버포드병변에서나타날수있는두꺼워진중관절와상완인대 (Cord-likeMGHL) 소견이관찰되었다. 견봉하공간및회전근개의이상소견은관찰되지않았다 (Fig. 1). 즉자기공명관절조영술에서는정상변형과병적인병변의차이를구별하기가쉽지않았다.따라서환자는4주간의보존적치료를통한경과관찰을시행하였다. 하지만4주후외래추시상증상호전이없어, 임상적으로SLAP 병변으로진단을내리고관절경적수술을시행하였다. 수술은전신마취하에좌측측와위자세에서시행하였다. 관절경검사상, 자기공명관절조영술에서SLAP 병변으로생각되었던부위는상완이두근장두가상부관절와순에위치하지않고, 상부관절낭및극상근건에부착되어있었다(Fig. 2A). 상완이두근장두는Hammock-like synovial sling에의해 덮여있는소견이관찰되었다(Fig. 2B). 자기공명 관절조영술상관찰되었던두꺼워진중관절와상완인대는관절경상에서는관찰되지않았다. 상완이두근장두가상부관절낭에부착하여상부관절낭과상완이두근장두부착부위사이에깊은주름(Sulcus)이 형성되어, 이부위가자기공명관절조영술에서SLAP 병변으로오인된것으로생각되었다. 하지만전방및후방관절낭은정상이었고,회전근개및관절와순의이상소견은없었다. 정상적인상완이두근장두주위의 sheath인지를감별하기위하여Synovial sling은 관절경적칼로제거하였다(Fig. 2C). Sling 제거후, 관절경소견에서도상완이두근장두가극상근건및상부관절낭에부착되어있었다. 따라서sheath가덮고있는정상소견이

Bone morphogenetic protein 2 (BMP2) was selected as a transgene to regenerate osteoporotic bone defects after several BMPs were tested using a bone formation study in nude mice. Human chondrocytes were transduced with a BMP2-containing retroviral vector, and single clones were selected. The cells were characterized over numerous passages for growth and BMP2 expression. The single clones were irradiated and tested for viability. BMP2 expression lasted for 3 weeks before dying off completely after approximately 1 month. Irradiated and non-irradiated transduced chondrocytes successfully healed fractures in osteoporotic rats induced by ovariectomy. The osteoinducing effect of irradiated cells was better than that of their non-irradiated counterparts or a chondrocytes-only control. This study showed that delivering BMP2 from the transduced and irradiated chondrocytes could be an effective and safe method of repairing osteoporotic bone fractures.

Little information is available on the role of environmental chemical exposure in oxidative stress. This study was designed to investigate whether exposure to environmental chemicals, such as polycyclic aromatic hydrocarbons, volatile organic compounds, bisphenol A or phthalates, induces oxidative stress in urban adult populations. A total of 960 adults dwelling in urban areas were evaluated between April and December 2005. To assess environmental chemical exposure, we measured urinary levels of 1-hydroxypyrene, 2-naphthol, hippuric acid, methyl hippuric acid, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-butyl phthalate and bisphenol A. Urinary malondialdehyde and 8-hydroxydeoxyguanosine were also measured to evaluate oxidative stress. Significant dose-responsive relationship was found between urinary concentrations of the chemical exposure biomarkers and oxidative stress levels in simple regression analyses (P

The mechanism of the adverse health effects of ambient particulate matter on humans has not been well-investigated despite many epidemiologic association studies. Measurement of personal exposure to particulate pollutants and relevant biological effect markers are necessary in order to investigate the mechanism of adverse health effects, particularly in fragile populations considered to be more susceptible to the effects of pollutants.We measured personal exposure to PM(2.5) and examined oxidative stress using urinary malondialdehyde three times in 51 preschoolers and 38 elderly subjects. A linear mixed-effects model was used to estimate PM(2.5) effects on urinary MDA levels.Average personal exposure of the children and elderly to PM(2.5) was 80.5 +/- 29.9 and 20.7 +/- 12.7 mug/m(3), respectively. Mean urinary MDA level in the children and the elderly was 3.6 +/- 1.9 and 4.0 +/- 1.6 mumol/g creatinine. For elderly subjects the PM(2.5) level was significantly associated with urinary MDA after adjusting for age, sex, BMI, passive smoking, day-care facility site, alcohol consumption, cigarette smoking, and medical history (heart disease, hypertension and bronchial asthma). However, there was no significant relationship for children.The elderly were more susceptible than young children to oxidative stress as a result of ambient exposure to PM(2.5). Identification of oxidative stress induced by PM(2.5) explains the mechanism of adverse health effects such as cardiovascular or respiratory diseases, particularly in the elderly.

Environmental tobacco smoking (ETS) is known to be associated with adverse pregnancy outcomes. The purpose of this study was to investigate the relationship between maternal exposure to ETS and oxidative stress for neonates, as well as the effect of maternal genetic polymorphisms, glutathione-S-transferase M1 (GSTM1) and GSTT1, on this relationship. We used the radioimmunoassay to measure the urinary concentration of cotinine in 266 pregnant women who denied smoking cigarettes during pregnancy and in their singleton babies. In addition, the urinary concentration of malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) were assessed using high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. We also extracted DNA from whole blood obtained from the mothers and then conducted polymerase chain reaction on the samples to determine the GSTM1 and GSTT1 genotypes. The maternal cotinine concentration was found to be significantly associated with the fetal cotinine concentration, particularly for mothers whose urine cotinine concentrations were above 120 microg/gcr (p0.01). The fetal urine cotinine concentration was also found to be significantly associated with the fetal urine MDA concentration (p0.01). When the null type maternal GSTM1 or the wild type GSTT1 was present, the maternal oxidative stress level increased significantly as the maternal continine concentration increased (MDA: p0.01; 8-OH-dG: p0.01). No significant relationships were found between maternal cotinine and fetal oxidative stress markers, however, the fetal MDA levels increased significantly as fetal cotinine levels increased. These results suggest that the maternal exposure to ETS affects the fetal urine cotinine concentration and induces production of maternal oxidative stress. In addition, maternal genetic polymorphisms of GSTM1 and GSTT1 may modify the oxidative stress by maternal exposure to ETS.

Background: Many studies have shown a consistent association between ambient air pollution and an increase in death due to cardiovascular causes. An increase in blood pressure is a common risk factor for a variety of cardiovascular diseases. However, the association between air pollution and blood pressure has not been evaluated extensively. Methods: In this cross-sectional study, we measured blood pressure in 10 459 subjects who had a health examination from 2001 to 2003, and calculated individual’s exposure to ambient levels of air pollutants. To evaluate the relationship between exposure to air pollutants and blood pressure with respect to season, we performed a multiple regression analysis, separately, according to season, controlling for individual characteristics and meteorological variables. Results: In the warm-weather season (July–September), particulate air pollutant of 10 ) and nitrogen dioxide (NO 2 ) concentrations were significantly associated with measures of blood pressure. During cold weather (October–December), blood pressure was significantly associated with sulphur dioxide (SO 2 ) and ozone (O 3 ) concentrations. The significant association between PM 10 or NO 2 and blood pressure disappeared during the cold-weather season. Conclusion: We found a seasonal variation for the association between ambient air-pollutant concentrations and blood pressure.

Background A localized non-surgical delivery of allogeneic human chondrocytes (hChonJ) with irradiated genetically modified chondrocytes (hChonJb#7) expressing transforming growth factor-β1 (TGF-β1) showed efficacy in regenerating cartilage tissue in our pre-clinical studies and human Phase I and II clinical trials. These previous observations led us to investigate the molecular mechanisms of the cartilage regeneration. Methods Genetically modified TGF-β1preprotein was evaluated by monitoring cell proliferation inhibition activity. The effect of modified TGF-β1 on chondrocytes was evaluated based on the type II collagen mRNA levels and the amount of glycosaminoclycan (GAG) formed around chondrocytes, which are indicative markers of redifferentiated chondrocytes. Among the cartilage matrix components produced by hChonJb#7 cells, type II collagen and proteoglycan, in addition to TGF-β1, were also tested to see if they could induce hChonJ redifferentiation. The ability of chondrocytes to attach to artificially induced defects in rabbit cartilage was tested using fluorescent markers. Results Throughout these experiments, the TGF-β1 produced from hChonJb#7 was shown to be equally as active as the recombinant human TGF-β1. Type II collagen and GAG production were induced in hChonJ cells by TGF-β1 secreted from the irradiated hChonJb#7 cells when the cells were co-cultured in micro-masses. Both hChonJ and hChonJb#7 cells could attach efficiently to the defect area in the rabbit cartilage. Conclusions This study suggests that the mixture (TG-C) of allogeneic human chondrocytes (hChonJ) and irradiated genetically modified human chondrocytes expressing TGF-β1 (hChonJb#7) attach to the damaged cartilage area to produce type II collagen-GAG matrices by providing a continuous supply of active TGF-β1.

Background The contribution of the metal components of particulate pollutants to acute respiratory effects has not been adequately evaluated. Moreover, little is known about the effects of genetic polymorphisms of xenobiotic metabolism on pulmonary function. Objectives This study was conducted to assess lung function decrement associated with metal components in particulate pollutants and genetic polymorphisms of glutathione S-transferase M1 and T1. Methods We studied 43 schoolchildren who were in the 3rd to 6th grades. Each student measured peak expiratory flow rate three times a day for 42 days. Particulate air concentrations were monitored every day, and the concentrations of iron, manganese, lead, zinc, and aluminum in the particles were measured. Glutathione S-transferase M1 and T1 genetic polymorphisms were determined using DNA extracted from participant buccal washings. We used a mixed linear regression model to estimate the association between peak expiratory flow rate and particulate air pollutants. Results We found significant reduction in the peak expiratory flow rate after the children’s exposure to particulate pollutants. The effect was shown most significantly 1 day after exposure to the ambient particles. Manganese and lead in the particles also reduced the peak expiratory flow rate. Genetic polymorphisms of glutathione S-transferase M1 and T1 did not significantly affect peak expiratory flow rate. Conclusions This study demonstrated that particulate pollutants and metals such as manganese and lead in the particles are associated with a decrement of peak expiratory flow rate. These effects were robust even with consideration of genetic polymorphisms of glutathione S-transferase.

The purpose of this study was to investigate the efficacy of cartilage regeneration when using a mixture of transforming growth factor-beta1 (TGF-beta1)-producing human chondrocytes (hChon-TGF-beta1) and primary human chondrocytes (hChon) ("mixed cells"), compared with either hChon-TGF-beta1 or hChon cells alone. Specifically, mixed cells or hChon cells were first injected intradermally into the backs of immune-deficient nude mice to test the feasibility of cartilage formation in vivo. Both the mixed cells and the hChon-TGF-beta1 cells alone induced cartilage formation in nude mice, whereas hChon cells alone did not. To further test the efficacy of the cells in generating cartilage, an artificially induced partial thickness defect of the femoral condyle of a rabbit knee joint was loaded with hChon-TGF-beta1 cells with or without mixing additional untransduced hChon cells, and hyaline cartilage regeneration was observed at 4 or 6 weeks. The efficiency of complete filling of the defect and the quality of tissue generated after implanting were evaluated on the basis of a histological grading system modified from O'Driscoll et al. (J. Bone Joint Surg. 70A, 595, 1988). Significantly, mixed cells (14.2 +/- 0.9) produced significantly better results than hChon-TGF-beta1 (9.0 +/- 1.7) or hChon (8.0 +/- 1.8) cells alone. Histological and immunohistochemical staining of the newly repaired tissues produced after treatment with either mixed cells or hChon-TGF-beta1 cells alone showed hyaline cartilage- like characteristics. These results suggest that the implantation of mixed cells may be a clinically efficient method of regenerating hyaline articular cartilage.

The purpose of this study is to evaluate the role of maternal oxidative stress in lowering neonatal birth weight. Women (N=261) with singleton pregnancy were analyzed for biomarker levels of oxidative stress after recruitment at the time of hospitalization for delivery in Korea between 2000 and 2001. Among the neonates, 247 births were full-term infants and 14 births were pre-term infants. Biomarkers measured for oxidative stress were maternal urinary 8-hydroxydeoxyguanosine (8-OH-dG) and malondialdehyde (MDA). The women with pre-term infants had higher concentrations of urinary 8-OH-dG and MDA than those with full-term babies. The concentrations of maternal urinary 8-OH-dG and MDA were inversely associated with birth weight of full-term deliveries after adjusting for potential confounders including maternal age, body mass index, dietary intake, alcohol consumption, smoking exposure, occupational status, and neonatal sex (P0.05). This study demonstrates that increase of 8-OH-dG and MDA concentrations in urine of pregnant women were associated with reduced birth weight in full-term deliveries.

Objectives: Exposure to air pollution has been reported to be associated with increase in pulmonary disease. The aims of the present study were to examine the use of personal nitrogen dioxide (NO2) samplers as a means of measuring exposure to air pollution and to investigate the relationship between personal exposure to air pollution and pulmonary function. Methods: We measured individual exposures to NO2 using passive personal NO2 samplers for 298 healthy university students. Questionnaire interview was conducted for traffic-related factors, and spirometry was performed when the samplers were returned after 1 day. Results: Personal NO2 concentrations varied, depending on the distance between residence and a main road (P=0.029). Students who used transportation for more than 1 h were exposed to higher levels of NO2 than those using transportation for less than 1 h (P=0.032). In terms of transportation, riding in a bus or subway caused significantly higher exposure than not using them (P=0.046). NO2 exposure was not significantly associated with forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1) but was associated with the ratio of FEV1/FVC and mid-expiratory flow between 25% and 75% of the forced vital capacity (FEF25–75) (P

Various iridium complexes consisting of phenylpyrazole (ppz) ligands and isoquinolinecarboxylic acids (iq) as ancillary ligands were designed by energy band-gap calculations via ab initio calculations and synthesized to give rise to various emission wavelengths as expected. Fine color tuning was achieved through varying the position of the methyl substituent on the phenylpyrazole moiety with HOMO electron densities. Additional color tuning was made possible by altering the LUMO through the use of different ancillary ligands such as 1-isoquinolinecarboxylic acid (1iq) and 3-isoquinolinecarboxylic acid (3iq).

To evaluate contribution of polymorphisms of the XRCC1 gene to the risk of colorectal cancer, we conducted a case-control study of 209 colorectal cancer cases and 209 age- and gender-matched controls in the Korean population. We tested the hypothesis by constructing allele combinations with known SNP. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in lymphocyte DNA by PCR-RFLP. We observed an increased risk of colorectal cancer associated with the 399Gln allele. The odds ratio (OR) was 1.61 (95% confidence interval [CI] 1.09–2.39) for the 399Gln allele. When combined allele-specific OR were calculated after estimating frequencies, 3 common allele combinations were found to be associated with an increased risk of colorectal cancer. The OR for the 194Trp-280Arg-399Arg was 1.48 (95% CI 5 1.06– 2.07) using 194Arg-280Arg-399Arg as the reference. The OR for the 194Arg-280His-399Arg and the 194Arg-280Arg-399Gln were 1.78 (95% CI 5 1.09–2.89) and 1.78 (95% CI 5 1.23–2.59), respectively. Analysis after controlling for smoking, exercise and dietary habits indicated that alcohol consumption (� 80 g/week) is a significant risk factor of colorectal cancer (OR 5 2.60, 95% CI 5 1.46– 4.62). An increased risk for colorectal cancer was identified in alcohol drinkers with the risky allele combinations. Our results suggest that polymorphisms in the XRCC1 genes may contribute to colorectal cancer susceptibility, and some evidence was obtained of a genetic modification for the relationship between alcohol intake and colorectal cancer. ' 2005 Wiley-Liss, Inc.

One of the most important factors in the production of cartilage is transforming growth factor beta1 (TGF-beta1). To obtain sustained release of TGF-beta1, a cell-mediated gene therapy technique was introduced. We infected chondrocytes with a retroviral vector carrying the TGF-beta1 gene. The single clone derivative showed sustained TGF-beta1 secretion. It also showed constitutive type II collagen expression. Whereas the TGF-beta1 protein itself is unable to induce formation of cartilage in vivo, human chondrocytes engineered to express a retroviral vector encoding TGF-beta1 showed cartilage formation in vivo when cells were injected into nude mice intradermally. These data suggest that cell-mediated gene therapy using TGF-beta1 as a transgene would be a promising treatment for osteoarthritis.

Retroviral vectors have been widely used in gene therapy due to their simple genomic structure and high transduction efficiency. We report a construction of Moloney murine sarcoma virus (MoMSV) and Moloney murine leukemia virus (MoMLV) hybrid-based retroviral vectors with significantly improved efficiency of transgene expression after stable incorporation into the host genome. In these vectors, the residual gag gene coding sequence located in the extended region of packaging signal was removed. These vectors, therefore, contain no coding sequence for the gag, pol, or env gene that can be used for homologous recombination with sequences introduced in the packaging system for a recombinant competent retrovirus (RCR) generation. A strong splice acceptor site obtained from the exon/intron junction of either the chimpanzee EF1-alpha gene or the human CMV major immediate early gene was placed downstream of the MoMSV packaging signal (Psi), significantly improving the efficiency of transgene expression. The 5' LTR U3 sequence was replaced with an extended human CMV major immediate early gene enhancer/promoter for a strong expression of full-length messages from the viral backbone, helping to maintain high levels of viral titer. These newly developed retroviral vectors should facilitate RCR-free gene transfer with significantly improved efficacy in clinical gene therapy trials.

The regeneration of hyaline articular cartilage by cell-mediated gene therapy using transforming growth factor beta(1) (TGF-beta(1))-producing fibroblasts (NIH 3T3-TGF-beta(1)) has been reported previously. In this study, we investigated whether TGF-beta(1)-producing fibroblasts irradiated with a lethal dose of radiation are still capable of inducing the regeneration of hyaline articular cartilage. NIH 3T3TGF-beta(1) fibroblasts were exposed to doses of 20, 40, or 80 Gy, using a irradiator, and then injected into artificially made partial defects on the femoral condyle of rabbit knee joints. The rabbits were killed 3 or 6 weeks postinjection and hyaline articular cartilage regeneration was evaluated by histological and immunohistochemical staining (n = 5 per each group). Irradiated NIH 3T3-TGFbeta(1) fibroblasts started to die rapidly 3 days after irradiation; moreover, the kinetics of their viability were similar regardless of the radiation intensity. TGF-beta1 expression, measured by ELISA, showed that the TGF-beta(1) protein produced from the irradiated cells peaked 5 days after irradiation and thereafter declined rapidly. Complete filling of the defect with reparative tissue occurred in all the groups, although variations were observed in terms of the nature of the repair tissue. Histological and immunohistochemical staining of the repair tissue showed that the tissue newly formed by irradiated NIH 3T3-TGF-beta(1) fibroblasts after exposure to 20 Gy had hyaline cartilage-like characteristics, as was observed in the nonirradiated controls. On the other hand, the repair tissue formed by NIH 3T3-TGF-beta(1) fibroblasts irradiated with 40 or 80 Gy showed more fibrous cartilage-like tissue. These results suggest that TGF-beta(1)-producing fibroblasts irradiated up to a certain level of lethal dose (i.e., 20 Gy) are able to induce normal-appearing articular cartilage in vivo. Therefore, irradiated heterologous cell-mediated TGF-beta(1) gene therapy may be clinically useful and an efficient method of regenerating hyaline articular cartilage.

It has been hypothesized that transforming growth factor-beta1 (TGF-beta1) signalling is involved in erectile dysfunction (ED). This study was undertaken to elucidate in detail whether expression of TGF-beta1 and its type II receptor is clinically related to various causes of ED. Fifty-four patients with ED and 24 potent men were the subjects of this study. After multidisciplinary work-up, the ED was classified as psychogenic (n = 6), neurogenic (n = 15), or vasculogenic (n = 33). In every subject, percutaneous cavernous biopsy was performed using a Biopty gun. Masson's trichrome staining was used to quantitate collagen fibres and immunohistochemical staining to evaluate both TGF-beta1 and its type II receptor by scoring the intensity of immunoreactivity (score 0-6). Collagen fibres were significantly more abundant in men with vasculogenic ED (72.7 +/- 17.7%) than in control subjects (43.3 +/- 11.2%) or those with psychogenic (45.0 +/- 12.2%) or neurogenic (51.3 +/- 20.3%) ED (p < 0.01). Expression of TGF-beta1 was significantly greater in vasculogenic ED (4.3 +/- 1.3) than in the control subjects (2.4 +/- 0.9) or psychogenic ED (2.0 +/- 0.6) groups (p < 0.01). Type II receptor expression was also significantly increased in vasculogenic ED (3.9 +/- 1.3) compared with control (2.2 +/- 0.7) and psychogenic (2.2 +/- 0.8) or neurogenic (2.6 +/- 1.3) ED (p < 0.01). Of the ED groups, both the hyperlipidaemia and the atherosclerosis patients showed significantly more fibrosis than those without the condition (p < 0.05). The abundance of collagen fibres correlated well with both TGF-beta1 expression (gamma = 0.81; p < 0.001) and receptor II expression (gamma = 0.83; p < 0.001). These results suggest that TGF-beta1 and its receptor II pathway are involved in cavernous fibrosis and ED in man. Patients with vascular risk factors such as hyperlipidaemia and atherosclerosis are liable to ED by activation of this pathway.

Shipbuilding workers are exposed to a variety of genotoxic compounds including polycyclic aromatic hydrocarbons (PAHs). A limited number of studies have been conducted to evaluate biomarkers related to PAH exposure in painters in the shipyard industry. We examined this in 208 workers recruited from a shipyard located in South Korea. Employees were grouped into three exposure groups: (1) 111 painters using coal tar paints, (2) 70 painters using general paints, and (3) 27 on-site controls using no paints. Levels of urinary 1-hydroxypyrene glucuronide (1-OHPG), as internal dose of PAH exposure, were measured by synchronous fluorescence spectroscopy. Glutathione S-transferase (GST) M1 and T1 genotypes were assessed by a multiplex polymerase chain reaction (PCR)-based method, aromatic-DNA adducts in peripheral white blood cells were measured by 32P-postlabeling, and glycophorin A (GPA) variant frequencies in red blood cells were assessed by flow cytometry. Information on demographic characteristics, smoking habits, diet, job title and use of personal protective equipment (e.g. respiratory and dermal) were collected by self-administered questionnaire. Average urinary 1-OHPG levels in coal tar paint (2.24 micromol/mol creatinine) and general paint (1.38 micromol/mol creatinine) users were significantly higher than in on-site controls (0.62 micromol/mol creatinine) (P