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Background To establish the consensus about the conditions for undertaking clinical trials in xenocorneal transplantation in Korea, specific issues regarding the xenocorneal transplantation on ethical and regulatory aspects are addressed, and the guidelines to conduct clinical trial of the xenocorneal transplantation are proposed. Method and Results Chapter 1 reviews the key ethical requirements and progress of a Korean regulatory framework for clinical trials of xenocorneal transplantation. Chapters 2-7 provide recommendations on source pigs, quality control of porcine corneal procurement, preclinical efficacy required to justify a clinical trial, strategies to prevent transmission of porcine endogenous retrovirus ( PERV), patient selection for clinical trials, and informed consent in xenocorneal transplantation using either cellularized or decellularized porcine graft, which are essentially based on the International Xenotransplantation Association ( IXA) islet xenotransplantation consensus statement. The consensus statement of the inclusion criteria for the patients' selection has been made by the executive board members in Korean External Eye Disease Society. Conclusions This consensus statement will be a good initiative for Korean Food and Drug Administration to discuss final regulatory guidelines in conducting clinical trials of xenocorneal transplantation in Korea and for International Xenotransplantation Association to develop International Consensus Standards of Xenocorneal Transplantation. [ABSTRACT FROM AUTHOR]

The BK virus ( BKV) can be reactivated with immunosuppressive treatment in renal allograft recipients, which can result in interstitial nephritis ( BKV-associated nephropathy, BKVAN) and lead to renal allograft failure. Recently, leflunomide has been reported in some case series of BKVAN with favorable results. Most studies have included only adult patients, we herein report a pediatric case and include a literature review. The patient was a nine-yr-old female with end-stage renal disease due to hypoxic kidney injury. A deceased donor renal transplant was performed and good initial allograft function was achieved following treatment with prednisolone, tacrolimus and mycophenolate mofetil. The serum Cr level increased to 1.6 mg/dL over the following four-month period. A kidney biopsy revealed pathologic findings of acute cellular rejection and BK nephropathy. After methylprednisolone pulse therapy was administered to control acute rejection, the tacrolimus dose was reduced, and intravenous immunoglobulin treatment and leflunomide therapy were administered to control the BKVAN. Over the following 18 months, the viral load steadily decreased and remained below 100 copies/mL in the plasma. Leflunomide therapy in addition to a reduction of the immunosuppressive therapies resulted in a significant decline in the BK viral load without further deterioration of renal function. [ABSTRACT FROM AUTHOR]

Background Animal training prior to beginning an experiment is an essential procedure and a very important course because it may affect the results of hematologic and hormonal variables and the functions influenced by those factors. Because this training inevitably causes animal stress, we wondered how much time is needed for untrained monkeys to recover from stresses associated with experimental training. Methods We measured the hematological and stress hormonal (e.g., cortisol) changes on weekly basis before and after experimental monkey chair training in newly acquired rhesus monkeys. Results The neutrophil-to-lymphocyte (N/L) ratio significantly increased during the initial phase of the training and then gradually decreased after 3 weeks. Elevated serum cortisol levels in the initial phase also significantly decreased after 3 weeks of chair training. Conclusions We conclude that at least a 3-week period is needed in monkey chair training for recovery from training stress. These results suggest that many researchers using nonhuman primates should provide enough time (>3 weeks) for adaptation to the experimental environment prior to beginning a study. [ABSTRACT FROM AUTHOR]

The outcomes of expanded criteria donor ( ECD) kidneys have been reported to be inferior compared with standard criteria donor ( SCD) kidneys. However, the graft survival rate of ECD is not so inferior to SCD in Korea. The purposes of this study were to compare the outcomes of ECD kidneys with SCD kidneys and identify the influencing factors. We retrospectively studied 143 deceased donor transplants from August 2006 to June 2010. The patients were divided into SCD (n = 117) and ECD (n = 26) by UNOS criteria. The one- and three-yr graft survival rates of SCD and ECD (99.1% and 94.4% vs. 100% and 92.9%, respectively, p = 0.15) were not significantly different between groups. The mean cold ischemic time ( CIT) was 3.8 ± 2.2 h. When compared the outcome of ECD kidneys with data reported by Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients ( OPTN/ SRTR) (one- and three-yr graft survival rate: 86.7% and 73.2%), the graft survival rate of our center was superior. In OPTN/ SRTR data, transplant with CIT shorter than 11 h was only 20%. The outcomes of ECD grafts are outstanding and comparable with SCD grafts in our center, and the only distinguishing factor is markedly short CIT. Finishing the allocation before organ recovery and immediate operations after recovery could shorten the CIT. [ABSTRACT FROM AUTHOR]

Abstract: Maximum engraftment of transplanted islets is essential for the clinical application of a subcutaneous site. Significant barriers to the current approaches are associated with their low effectiveness, complexity and unproven biosafety. Here, we evaluated and optimized a fibrin–islet composite for effective glycemic control in a subcutaneous site whose environment is highly hypoxic due to low vascularization potential. In the setting of xenogeneic porcine islet transplantation into the subcutaneous space of a diabetic mouse, the in vivo islet functions were greatly affected by the concentrations of fibrinogen and thrombin. The optimized hydrogel-type fibrin remarkably reduced the marginal islet mass to approximately one tenth that of islets without fibrin. This marginal islet mass was comparable to that in the setting of the subcapsular space of the kidney, which is a highly vascularized organ. Highly vascularized structures were generated inside and on the outer surface of the grafts. A hydrogel-type fibrin–islet composite established early diabetic control within an average of 3.4days after the transplantation. In the mechanistic studies, fibrin promoted local angiogenesis, enhanced islet viability and prevented fragmentation of islets into single cells. In conclusion, in situ application of hydrogel-type fibrin–islet composite may be a promising modality in the clinical success of subcutaneous islet transplantation. [Copyright &y& Elsevier]

Lee J-I, Shin J-S, Lee J-E, Jung W-Y, Lee G, Kim M-S, Park C-G, Kim S-J. Reference values of hematology, chemistry, electrolytes, blood gas, coagulation time, and urinalysis in the Chinese rhesus macaques ( Macaca mulatta). Xenotransplantation 2012; 19: 244-248.. © 2012 John Wiley & Sons A/S. Abstract: Background: Due to increasing preclinical study using the rhesus monkeys, the physiological data of these monkeys are very important for the objective evaluation of experimental results. Here, we report the physiological values of the Chinese rhesus monkeys acclimated under a well-controlled laboratory environment. Methods: Seventy healthy rhesus monkeys of both genders (29 males and 41 females) were used in this study. Available data on hematology, serum biochemistry, electrolytes, blood gas, coagulation time, urinalysis, water consumption, urine volume, and body weight were examined. Results: The lymphocyte values were 1.5-2.5 times higher than the neutrophil values in both genders. In serum biochemistry, there was no significant difference between the two genders. Interestingly, the values of alkaline phosphatase from the monkeys were very high. According to isoenzyme analysis, the percentage of alkaline phosphatase that originated from the bone was 60%, and this value was significantly higher than that from the liver (39%, P = 0.020). Conclusion: Physiological data are very important parameters that can be directly and indirectly related to organ function (e.g. islet, kidney, liver, heart, etc.) in the transplantation model. In this respect, our data constitute valuable references for preclinical study using the Chinese rhesus monkeys. [ABSTRACT FROM AUTHOR]

Background. Idiopathic focal segmental glomerulosclerosis (FSGS) occurring at young age is known to predispose to poor graft outcome, but the outcome of adulthood-onset FSGS (A-FSGS) has not been thoroughly investigated. Here, we compared the graft outcomes between kidney recipients with A-FSGS and childhood-onset FSGS (C-FSGS). Methods. We enrolled 47 A-FSGS recipients and 60 C-FSGS recipients with an onset age of ≤15, from four of the largest transplant centers in Korea. Results. The baseline characteristics were similar between two groups. The 1- and 3-year cumulative recurrence rates were 20.0 and 22.1%, respectively. FSGS was recurrent in 19 C-FSGS patients [median duration, 2 months (interquartile range, IQR, 1–35)], and 11 patients had recurrent disease in A-FSGS [5 months (IQR, 3–37)]. The recurrence rate was similar between two groups (P = 0.126). The 5- and 10-year graft survival rates were 90.0 and 78.5%, respectively. The overall graft survival rates were not different between two groups. After adjusting baseline characteristics, the development of major outcomes was similar between two groups except acute rejection that was more frequent in A-FSGS. The age of disease onset did not affect recurrence in both groups. While grafts with recurrence had poorer graft survival in the A-FSGS group (P = 0.005), the recurrence was not associated with graft loss in the C-FSGS group (P = 0.558). Conclusions. The onset age did not affect the graft outcome in patients with FSGS, and the recurrence significantly affected graft survival in A-FSGS. Therefore, the main focus should aim for the management of recurrence. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Ischemic lesion growth may be a surrogate marker of clinical outcome, but no such interrelationship after thrombolysis has yet been determined. We evaluated the association between early infarct growth on diffusion-weighted imaging (DWI) and long-term clinical outcome after thrombolysis. Methods: We retrospectively reviewed outcomes in patients with acute middle cerebral artery territory stroke who had been treated with intravenous tissue plasminogen activator or intra-arterial urokinase. DWI lesion volumes were measured at baseline and within 7days, and the difference was calculated. Clinical outcome was evaluated using the modified Rankin Scale (mRS) at 3months. Good and poor clinical outcomes were defined as: a) mRS 0–1 vs. mRS 2–6, b) mRS 0–2 vs. mRS 3–6, and c) responder analysis which was influenced by the baseline National Institutes of Health Stroke Scale (NIHSS) scores: good and poor outcomes were defined as mRS 0 vs. mRS 1–6 if the baseline NIHSS score was <8, mRS 0–1 vs. mRS 2–6 if the NIHSS score was 8–14, and mRS 0–2 vs. mRS 3–6 if the NIHSS score was >14. The relationship between the ischemic lesion volume change and clinical outcome was explored. The cut-off value of infarct growth predicting long-term outcome was estimated using receiver operating characteristic analysis. Results: Of the 81 patients included, 67 (82.7%) showed lesion growth, and absolute growth was significantly related to poor outcomes (P<0.001 all for mRS 2–6, mRS 3–6, and responder analysis). Multivariate analysis showed that absolute lesion growth was an independent predictor of poor outcome, defined as mRS 2–6 (P=0.002; odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.10), mRS 3–6 (P=0.001; OR, 1.06; 95% CI, 1.02–1.10), and poor outcome by responder analysis (P=0.001; OR, 1.06; 95% CI, 1.03–1.10). The cut-off values of lesion growth that discriminated between good and poor outcomes were 14.11cm3 for mRS 2–6; 15.87cm3 for mRS 3–6; and 14.11cm3 in responder analysis. Conclusions: Early DWI lesion growth is an independent predictor of poor outcome after thrombolysis and may serve a potential surrogate marker of clinical outcome in acute stroke trials. [Copyright &y& Elsevier]

Lee KG, Lee H, Ha JM, Lee YK, Kang HJ, Park C-G, Kim SJ. Increased human tumor necrosis factor-α levels induce procoagulant change in porcine endothelial cells in vitro. Xenotransplantation 2012; 19: 186-195. © 2012 John Wiley & Sons A/S. Abstract: Background: Intravascular thrombosis and systemic coagulation abnormalities are major hurdles to successful xenotransplantation and are signs of acute humoral rejection. Increased expression of tissue factor (TF) is associated with the development of microvascular thrombosis in xenografts. To develop an effective strategy to prevent accelerated coagulation in xenografts, we investigated the mechanism by which porcine endothelial cells (PECs) become procoagulant after contact with human blood. Methods: The changes in TF mRNA levels and activity in PECs after incubation with 20% human serum or human bioactive molecules, including C5a, tumor necrosis factor-α (TNFα) and interleukin (IL)-1α, were evaluated using real-time PCR and the factor Xa chromogenic assay, respectively. The procoagulant changes in PECs by these agonists were evaluated by measuring the coagulation time of human citrated plasma suspended with PECs pretreated with each agonist. TF expression and coagulation times were also assessed in PECs transfected with short interfering RNA (siRNA) designed to knock down porcine TF. We also examined the production of proinflammatory cytokines in human whole-blood or plasma after contact with PECs, which were screened using the cytometric bead array system. TNFα levels were measured using ELISA in whole-blood after contact with PECs, with or without the addition of xenoreactive antibodies or C1 esterase inhibitor. Results: Porcine TF mRNA and activity in PECs were up-regulated in response to human TNFα and IL-1α but were not affected by C5a or 20% human serum. Up-regulation of TF expression by human TNFα or IL-1α shortened PEC-induced coagulation time, while siRNA-mediated knockdown of TF expression prolonged coagulation time. The incubation of PECs with human whole-blood led to a significant increase in human TNFα levels in the blood, which was promoted by the addition of xenoreactive antibodies and prevented by C1 esterase inhibitor. Conclusions: Human TNFα level increases in human blood after contact with PECs, which is attributed to xenoreactive antibody binding and subsequent complement activation. Human TNFα induces procoagulant changes in PECs with increased TF expression. This study suggests that human TNFα may be one of the mediators linking complement activation with procoagulant changes in the xenoendothelium. [ABSTRACT FROM AUTHOR]

Background: A substantial number of acute stroke patients do not respond immediately to aggressive intra-arterial (IA) recanalization therapy. The factors and outcomes associated with timing of recanalization after IA thrombolysis, however, have not yet been determined. Methods: Factors and outcomes in 75 acute ischemic stroke patients treated with IA urokinase (± intravenous tissue plasminogen activator) within 6 h of onset were retrospectively assessed. Immediate recanalization (IR) was assessed by the angiogram at the end of the IA procedure, and delayed (DR) and no (NR) recanalization were assessed by 5-day MR angiography. Modified Rankin Scale (mRS) scores were determined at 7 days and 3 months. Results: Of the 75 patients, 32 (42.7%) achieved IR, 21 (28%) achieved DR, and 22 (29.3%) showed NR. Good functional outcomes (mRS score ≤2) at 7 days and 3 months were observed in 59.4 and 62.5%, respectively, of the IR group, 14.3 and 38.1% of the DR group, and 22.7 and 27.3% of the NR group (p = 0.001 for 7 days, p = 0.028 for 3 months). Multivariate analysis showed that cardioembolism [odds ratio (OR), 3.74; 95% confidence interval (CI), 1.15-12.19] and middle cerebral artery occlusion (OR, 3.23; 95% CI, 1.04-10.04) were independent predictors of IR or DR compared with NR. Age (OR, 0.86; 95% CI, 0.77-0.95) and initial NIHSS score (OR, 1.20; 95% CI, 1.04-1.37) were independent predictors of DR compared with IR. Conclusions: Patients receiving IA thrombolysis show different clinical and radiological characteristics according to the timing of recanalization. Earlier identification of DR patients and their more efficient recanalization may improve overall clinical outcomes after IA thrombolysis. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Jin S-M, Shin JS, Kim KS, Gong C-H, Park SK, Kim J-S, Yeom S-C, Hwang ES, Lee CT, Kim S-J, Park C-G. Islet isolation from adult designated pathogen-free pigs: use of the newer bovine nervous tissue-free enzymes and a revised donor selection strategy would improve the islet graft function. Xenotransplantation 2011; 18: 369-379. © 2011 John Wiley & Sons A/S. Abstract: Background: In clinical trials using adult porcine islet products, islets should be isolated from the designated pathogen-free (DPF) pigs under the current good manufacturing practice (GMP) regulations. Our previous studies suggested that male DPF pigs are better donors than retired breeder pigs and histomorphometrical parameters of donor pancreas predict the porcine islet quality. We aimed to investigate whether the use of the newer bovine nervous tissue-free enzymes and a revised donor selection strategy could improve the islet graft function in the context of islet isolation with DPF pigs. Methods: Using 30 DPF pigs within a closed herd, we compared the islet yield of porcine islets isolated with Liberase PI (n = 11, as a historical control group), Liberase MTF C/T, which is a GMP-grade enzyme (n = 12), and CIzyme collagenase MA/BP protease (n = 7). We analyzed the relationship between the diabetes reversal rate of recipient NOD/SCID mice (n = 75) and histomorphometric parameters of each donor pancreas as well as donor characteristics. Results: Proportion of islets larger than 200 μm from the biopsied donor pancreas (P = 0.006) better predicted islet yield than age (P = 0.760) or body weight (P = 0.371) of donor. The proportion of islets larger than 200 μm from the biopsied donor pancreas was not related to the sex of the donor miniature pig (P = 0.358). The islet yield obtained with the three enzymes did not differ, even after stratification of the donor with the histomorphometric parameters of the biopsied donor pancreas and the sex of donor. The use of the newer bovine nervous tissue-free enzymes (P < 0.001), a higher proportion of large islets in donor pancreas (P = 0.006), and a male sex of the donor (P = 0.025) were independent predictors of earlier diabetes reversal. Conclusions: Use of the newer bovine nervous tissue-free enzymes including a GMP-grade enzyme resulted in better islet quality than that of islet isolated using Liberase PI. To obtain high-quality islet from DPF pigs, the donor should be male pig and histomorphometrical parameters from donor pancreas should be considered. [ABSTRACT FROM AUTHOR]

Abstract: Post-translational modification by small ubiquitin-like modifier (SUMO) is involved in several significant cellular events. In particular, SUMO-1 and SUMO-4 modifications of IκBα have been shown to be actively involved in NFκB regulation. However, among the SUMO family, the specific function of SUMO-2/3 remains relatively unknown. In addition, it is not clear whether SUMO-2/3 follows the same functional role as SUMO-1 and SUMO-4 during the activation of NFκB. In this study, we examined the influence of mouse SUMO-2 during the maturation of dendritic cells (DCs). Our results showed that the ectopic expression of SUMO-2 does not affect the cell surface expression of MHC class II molecule (Ab) and co-stimulatory molecules (CD80 and CD86), and the efficiency of antigen uptake. However, the ectopic expression of mouse SUMO-2 inhibited IL-12 secretion by blocking the translocation of the p65 subunit of NFκB into the nucleus, which led to the polarization of naïve CD4+ T cells to T helper 2 (Th2) shift in vitro. Further analyses showed that SUMO-2 directly modified IκBα. These results indicate that the functional role of SUMO-2/3 in the regulation of NFκB activity was conserved during evolution. [Copyright &y& Elsevier]

Abstract: Autophagy is an important process which maintains cellular homeostasis under stressful conditions such as starvation and pathogenic invasion. Previous observations have indicated that several cytokines are important regulators of the autophagic process. Among the various cytokines, IL-10 has a unique property which functions to suppress overall immunity. However, the functional role of IL-10 during the autophagic process has not been studied. In this study, we examined the effect of IL-10 during starvation induced autophagy of murine macrophages (J774). The results clearly indicated that IL-10 and IL-10 receptor signaling inhibits autophagy induction of murine macrophage. Further experiments revealed that IL-10 activates the class I phosphatidylinositol 3-kinase (PI3K) pathway, which results in the phosphorylation of p70S6K through the activation of Akt and a mammalian target of the rapamycin complex 1 (mTORC 1). These results will advance our understanding of the physiological function of IL-10 during the autophagic process of macrophage. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Although MRI may provide much information on brain pathology to aid in patient selection for thrombolysis, the concern remains that MRI screening may increase time-to-treatment. We hypothesized that CT-plus-MRI screening might be a valuable time-efficient alternative for selection of patients requiring thrombolysis. Methods: We reviewed acute stroke patients who received intravenous tissue plasminogen activator (tPA) (with or without intra-arterial urokinase) initiated within 3h of stroke between March 2004 and March 2007. MRI was the routine screening imaging employed until November 2005. Thereafter, CT-plus-MRI screening was performed; tPA of 0.6mg/kg was infused intravenously after exclusion of hemorrhage by CT screening, and subsequently a further decision on thrombolysis (i.e., intravenous tPA of 0.3mg/kg, or intra-arterial urokinase) was made after MRI screening. We compared times-to-treatment and clinical outcomes between MRI screening and CT-plus-MRI-screening groups, and identified factors associated with good clinical outcome (modified Rankin Scale ≤2 at 3months). Results: Eighty-nine patients were included in the analysis; 43 were MRI-screened, and 46 were CT-plus-MRI-screened. Although the MRI-screening group had a longer door-to-needle time (p <0.001), these patients showed better 3-month outcomes compared to CT-plus-MRI-screening group (p =0.01). Multivariate analysis showed that MRI screening (odds ratio 3.97, 95% confidence interval 1.30–12.17, p =0.02) was independently associated with a good outcome at 3months. In CT-plus-MRI-screening group, although time-to-initial imaging and time-to-tPA were shorter, time-to-MRI and time-to-additional thrombolysis were delayed. Conclusion: These results suggest that early patient selection using MRI may be more effective than reduction of times-to-treatment in improvement of thrombolytic outcomes. [Copyright &y& Elsevier]

Abstract: The purpose of our study was to evaluate the ultrasound features of suture granulomas at the thyroid bed after thyroidectomy for papillary thyroid carcinoma with an emphasis on their differentiation from locally recurrent thyroid carcinomas. We enrolled 14 suture granulomas in 10 patients and 20 locally recurrent carcinomas in 18 patients after thyroidectomy, confirmed by surgery (15 out of 20 recurrent carcinomas), or ultrasound-guided fine needle aspiration cytology (14 suture granulomas and 5 recurrent carcinomas). The ultrasound findings, including presence of internal echogenic foci suggesting calcification or suture material, were compared between the two groups. In the cases with internal echogenic foci, the size, number, distribution pattern, and the presence of a paired appearance were also evaluated. In result, most of the suture granulomas were irregular (n=13) and heterogeneous (n=9) (p <0.05). The incidence of internal echogenic foci was higher in suture granulomas (n=12) than in recurrent carcinomas (n=7) (p <0.05). The internal echogenic foci in all suture granulomas were clustered centrally or paracentrally, unlike those in recurrent carcinomas (p <0.05). Most of the echogenic foci in suture granulomas were larger than 1 mm in diameter (p <0.05) and had a paired appearance (p <0.05). Shape, heterogeneity, and the presence of central or paracentral internal echogenic foci are helpful criteria for differentiating suture granulomas from locally recurrent tumors in the thyroid bed. (E-mail: jeonghlee@hanmir.com) [Copyright &y& Elsevier]

Abstract: Introduction: Racial disparities in incidence rate as well as risk factors for venous thromboembolism (VTE) exist between Asian and Western populations. Moreover, predictors for recurrent VTE were not identified in Asians. Thus, this study was undertaken to investigate risk factors for recurrent VTE events in Korean people. Materials and Methods: Three hundred-three patients newly diagnosed as VTE were enrolled from Seoul National University Hospital. Recurrence rate based on risk factors for VTE were investigated. Cumulative incidence of recurrent VTE was calculated by the Kaplan and Meier method. Independent predictors for VTE were determined using Cox proportional hazards model. Results: After a median follow-up of 44 months, 24 (8%) of 303 patients relapsed for a total observation time of 1,217 patient-year. Cumulative incidences of recurrent VTE were 3% at 1 year, 10% at 5 years, and 18% at 8 years. Independent predictors for recurrent VTE were presence of residual thrombosis (hazard ratio [HR]=3.1, 95% confidence interval [CI] 1.0–9.3; p =0.044), antiphospholipid syndrome (APS) (HR=4.3, 95% CI 1.0–19.0; p =0.052), and age 50 years or younger (HR=2.5, 95% CI 1.0–6.6; p =0.053) by multivariate analysis. Residual thrombosis and APS remained predictive of recurrence by the anticoagulation-period stratified analysis. Conclusions: In contrast to Western populations, Korean patients with VTE had the lower recurrent rate. Extended anticoagulation is necessary for Korean patients with residual thrombosis or APS. [Copyright &y& Elsevier]

Abstract: Feature-based registration is an effective technique for clinical use, because it can greatly reduce computational costs. However, this technique, which estimates the transformation by using feature points extracted from two images may cause misalignments, particularly in brain PET and CT images that have low correspondence rates between features due to differences in image characteristics. To cope with this limitation, we propose a robust feature-based registration technique using a Gaussian-weighted distance map (GWDM) that finds the best alignment of feature points even when features of two images are mismatched. A GWDM is generated by propagating the value of the Gaussian-weighted mask from feature points of CT images and leads the feature points of PET images to be aligned on an optimal location even though there is a localization error between feature points extracted from PET and CT images. Feature points are extracted from two images by our automatic brain segmentation method. In our experiments, simulated and clinical data sets were used to compare our method with conventional methods such as normalized mutual information (NMI)-based registration and chamfer matching in accuracy, robustness, and computational time. Experimental results showed that our method aligned the images robustly even in cases where conventional methods failed to find optimal locations. In addition, the accuracy of our method was comparable to that of the NMI-based registration method. [Copyright &y& Elsevier]

The effective removal of acetaldehyde by humidified air plasma was investigated with a high throughput of contaminated gas in a sandwiched honeycomb catalyst reactor at surrounding ambient temperature. Here, acetaldehyde at the level of a few ppm was successfully oxidized by the honeycomb plasma discharge despite the harsh condition of large water content in the feed gas. The conversion rate of acetaldehyde increased significantly with the presence of catalysts coating on the surface channels. The increased conversion rate was also obtained with a high specific energy input (SEI) and total flow rate. Interestingly, the conversion changed negligibly under the acetaldehyde concentration range from 5 to 20 ppm. However, the conversion rate decreased toward increased water amount in the feed gas. Notably, about 60% of acetaldehyde in the feed was oxidized under SEI of 40 J/L at water amounts ≤ 2.5%, approximately 0.5 g/kWh for acetaldehyde removal. Also, the plasma-catalyst reaction was superior to the thermal reactive catalyst for acetaldehyde removal in airborne pollutants. In comparison with other plasma-catalyst sources for acetaldehyde removal, the energy efficiency under the condition is comparable. Moreover, the honeycomb plasma discharge features high throughput, avoiding pressure drop, and straightforward reactor configuration, suggesting potential practical applications. [Display omitted] • Generation of large humid air plasma volume by a sandwich honeycomb plasma reactor. • Capable of practical plasma application for acetaldehyde removal in atmosphere. • Treating high throughput of simulated indoor emission of acetaldehyde. • High efficiency acetaldehyde removal although humid conditions. [ABSTRACT FROM AUTHOR]

Abstract: The effects of nicotine on vascular endothelial cells have not been completely elucidated. We performed this study to assess the changes in cellular behaviors of human umbilical vein endothelial cells (HUVECs) treated with nicotine. We examined changes in cell count and morphology and assayed cellular migration with Boyden chamber and microcapillary tube formation in a Matrigel matrix following treatment with various concentrations of nicotine. Compared to the control, nicotine stimulated cell proliferation, migration, and tube formation at concentrations similar to those found in smokers. Although there were no specific morphological changes in HUVECs treated with nicotine at the concentration similar to that in smokers, at high concentration (10−4 M), morphological changes such as cytoplasmic vacuolization and irregular cell shape were observed, which were assumed to be the result of direct cytotoxicity of nicotine. In HUVECs, nicotine enhanced cellular proliferation, migration and angiogenesis in vitro, and thus caused a functional change, not a morphological change at a concentration similar to that in habitual smokers. [Copyright &y& Elsevier]

Abstract: Transglutaminase2 (TGase2) activates Rho-associated kinase (ROCK), an important mediator of ischemia–reperfusion (IR) injury, through polyamination of RhoA. Cystamine, an oxidized dimer of cysteamine inhibits the transamidation activity of TGase2. We examined whether addition of cystamine to an organ preservation solution protects rat cardiomyocyte cells (H9C2) from cell death in IR injury. H9C2 cells were stored under hypoxic conditions at 4°C in laboratory-made preservation solution (SNU) or SNU solution supplemented with cystamine (SNU-C1), and cell preservation in the two solutions was compared by measuring the release of lactate dehydrogenase. The cells were preserved more effectively in SNU-C1 than in SNU solution. Cystamine inhibited the intracellular activity of TGase2 which increased during cold storage or reoxygenation. The inhibition of TGase2 by cystamine reduced the polyamination of RhoA, the interaction between RhoA and ROCK2, and F-actin formation. Cystamine also prevented the activation of caspases during cold storage. These results suggest that addition of cystamine to the organ preservation solution significantly enhances cardiomyocytes preservation apparently by inhibiting TGase2-mediated RhoA-ROCK pathway and that TGase2 may play an important role in IR injury by regulating ROCK. [Copyright &y& Elsevier]

Background: T helper 1 (Th1)/T helper 2 (Th2)-biased cytokine regulation may be another reason that neonates are much more susceptible to infectious disease than are adults. Objectives: We attempted to determine the ability of neonatal mice to direct the Th1 phenotype against Listeria monocytogenes (LM), because LM, an intracellular Gram-positive bacterium, induces profound cellular immunity by Th1 cells in vivo. Methods: In order to determine whether neonatal mice evidence strong Th1 activity during LM infection, neonatal mice were compared with adult mice with regard to susceptibility to LM, cytotoxic T lymphocyte activity, and cytokine profiles. Neonatal gene profiles relevant to Th1 and Th2 differentiation during LM infection were also compared between neonatal and adult mice, via real-time PCR and RT-PCR. Results: Neonatal mice were found to be far more susceptible to LM infection than adult mice, due to a lack in the induction of cytotoxic T cell activity, coupled with poor IFN-γ secretion. Further, LM-infected neonatal mice evidenced much lower levels of expression of Th1-type immune components, including IL-12, IFN-γ, Delta-4 and T-bet, as compared to those features in adult mice. These results may be due to the comparably lower expressions of mannose-bind lectins and some of toll-like receptors (TLRs) such as TLR-5, -6 and -9, necessary mediators to develop Th1 immune responses. Conclusions: Neonatal mice may not mount an adequate Th1 type immune response due to a significantly lower expression of Th1-type immune components as compared to adult mice, even when forced into a Th1-prone environment. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the ultrasonographic findings and performed ultrasonography-guided fine-needle aspiration biopsy of a newly detected nodule in the thyroid bed of 38 patients with postoperative thyroid carcinoma. Detection of a marginal irregularity, microcalcification, or a shape not parallel to the surrounding tissue plane might allow the identification of recurrent thyroid carcinoma from other benign pathologies mimicking local tumor recurrence. [Copyright &y& Elsevier]

Abstract: Upon antigenic stimulation, CD1d-restricted NKT cells quickly secrete large amounts of cytokines. This prompt response demonstrates that CD1d-restricted NKT cells may potentially prove to be useful therapeutic agents for the treatment of many diseases. Despite the clinical importance of CD1d-restricted NKT cells, the regulating mechanisms of this unique T cell population remain to be defined. We found murine LAG-3 is inducible on CD1d-restricted NKT cells as the result of a variety of stimulants such as concanavalin A (con A) and anti-CD3. Also, antigen-specific CD1d stimulation can elicit LAG-3 in CD1d-restricted NKT cells. Moreover, ectopic LAG-3 expression on CD1d-restricted NKT cells results in cell cycle arrest in the S phase. These results show that LAG-3 signaling on activated CD1d-restricted NKT cells may down-modulate NKT cell proliferation. [Copyright &y& Elsevier]

Branch occlusion of the anterior cerebral artery (ACA) is regarded as a part of Moyamoya disease. The purpose of this study is to define the ACA steal phenomenon (SP) in Moyamoya disease and to evaluate temoporal changes according to the disease progression. From 139 Moyamoya patients we defined ACASP as narrowing of the ipsilateral A1-2 junction while preserving the anterior communicating artery and supplying the contralateral ACA cortical branches with the development of leptomeningeal collaterals by the ipsilateral middle cerebral artery into the hypoperfused ipsilateral ACA territory. Direction of the steal related to the stage in both hemispheres by Suzuki classification was statistically analyzed using the binomial test based on binomial distribution. Follow-ups of ACASP were evaluated in five patients. We identified ACASP in 13 (9%) patients (male:female=7:6, mean age 18 years, range: 2-58 years) of the 139 study patients. The presenting pattern was ischemic in 12 and hemorrhagic in one. The direction of SP occurred from the hemisphere in the lower to the higher stage of Suzuki classification (two-tail P value=0.0002). After revascularization surgery, ACASP disappeared or diminished. ACASP may occur in bilaterally different stages of Moyamoya disease as a transient self-adaptive process. It regresses after revascularization surgery. [ABSTRACT FROM AUTHOR]

Comprehensive speech/language studies revealed mild dysarthria with limited lateral tongue movement and competent language ability except mild difficulty in repeating sentences. The data of fMRI showed the preponderant involvement of the right frontal in sentence completion and bilateral temporal areas in verb generation task (Fig. The arrows indicate the atypical areas activated during the language tasks: the right frontal on sentence completion task and bilateral temporal areas on verb generation task. [Extracted from the article]

Abstract: We report three cases of branchial cleft anomalies demonstrated by multidetector computed tomography (MDCT) fistulography. Multiplanar reformatted images using MDCT were excellent in delineating the whole fistulous tract and its surrounding structures. MDCT fistulography was very helpful in the diagnosis and surgical planning for sinus and fistula of branchial cleft anomalies. [Copyright &y& Elsevier]

Abstract: We describe MR imaging features of discal cyst of the lumbar spine in nine patients who presented with low back pain and leg pain. Discal cyst of the lumbar spine has characteristic MR imaging features different from other epidural cysts: a ventrolateral extradural cyst attached to a herniated lumbar disc, consisting of a thick fibrous capsule without disc material, and having occasional extension into the lateral recess with rim enhancement on contrast-enhanced MR imaging. [Copyright &y& Elsevier]

Abstract: Objective: Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted from macrophages locally in atheromas and if it affected vascular cell function in human. Methods and results: Immunohistochemical staining of human vessels showed that aortic aneurysms exhibited resistin-positive staining areas along macrophage infiltration, while normal arteries and veins did not. Co-localization of resistin and CD68 (a marker for macrophages) was observed in immunofluorescent double staining of aneurysms. Resistin mRNA was expressed much higher in cultured monocytes/macrophages than in human vascular smooth muscle cells (VSMCs) and human umbilical venous endothelial cells (HUVECs). This suggested that the resistin in aneurysms originates from macrophages within the vessels. To determine the effects of resistin on atherosclerosis, HUVECs and human VSMCs were incubated with resistin (10–100 ng/mL for 4∼24 h). In HUVECs, plasminogen activator inhibitor (PAI)-1 release was assayed by ELISA, while the PAI-1 and endothelin (ET)-1 mRNA levels were analyzed by Northern blotting. Both were increased significantly with resistin treatment by factors of 1.3–2.5 (p <0.05). Migratory activity of VSMCs measured by scratched wound assay also increased significantly (1.6 times, p <0.05). In summary, macrophages infiltrating atherosclerotic aneurysms secrete resistin, and resistin affects endothelial function and VSMC migration. Conclusions: Resistin secreted from macrophages may contribute to atherogenesis by virtue of its effects on vascular endothelial cells and smooth muscle cells in humans. [Copyright &y& Elsevier]

Abstract: Removal characteristics of polycyclic aromatic hydrocarbons (PAHs) from low-permeable soil using a surfactant-enhanced electrokinetic (EK) process were investigated. Phenanthrene and kaolinite were selected as a representative PAH and a model soil. A nonionic surfactant, alkyl polyglucosides (APG), and an anionic surfactant, Calfax 16L-35, were used to enhance the solubility of phenanthrene. The two surfactants showed similar solubilization capacities for phenanthrene, while only APG was affected by sorption. When surfactants were applied to EK process, the electrical potential gradient was lower than that of water. The electroosmotic flow (EOF) decreased as the concentration of surfactant increased. In the case of APG, the removal efficiency of phenanthrene increased with the surfactant concentration. The APG micelles containing phenanthrene easily migrated to the cathode reservoir by EOF. On the other hand, Calfax 16L-35 did not enhance the removal efficiency even at the highest concentration, because most of Calfax 16L-35 remained in soil, and only small amount existed in effluent. It was thought that, during electrokinetic process, Calfax 16L-35 was adsorbed onto soil and the migration of the surfactant from cathode to anode was superior to EOF due to anionic charges of Calfax 16L-35. A nonionic surfactant, APG, seems to be suitable for surfactant-enhanced electrokinetic remediation. [Copyright &y& Elsevier]

For categorizing the presenting neurological symptoms in Takayasu''s arteritis (TA) and correlating to the imaging findings of cerebral angiography, we retrospectively reviewed the angiographies of 27 patients presented with stroke, transient ischemic attack (TIA), visual disturbance, and/or dizziness. Neurological manifestations of TA resulted from decreased blood flow due to a steno-occlusive lesion and/or shifting of blood flow, thromboembolism, or hypertension. The pattern analysis of neurological manifestations related to specific arterial involvement is mandatory in understanding neurological manifestations of this systemic disease. [Copyright &y& Elsevier]

Human cytomegalovirus UL18, a MHC class I homologue, is known to serve as a natural killer cell (NK) decoy and to ligate NK inhibitory receptors to prevent lysis of an infected target cell. To explore whether the cell surface expression of UL18 represents a potential immune suppressive approach to evade NK-mediated cytotoxicity in the prevention of xenograft rejection, we examined the effect of the UL18 expression in vitro upon human NK-mediated cytotoxicity against swine endothelial cells (SECs). UL18 expression on SECs by a retroviral vector (PLNCX2) significantly suppressed NK-mediated SEC lysis by approximately 25–100%. The protective effect of UL18 could be mediated through ILT-2 inhibitory receptor on NKs. Additionally, the interaction between UL18 and NKs resulted in the significant reduction of IFN-γ production. This study demonstrates that UL18 can serve as an effective tool for the evasion of NK-mediated cytotoxicity and for the inhibition of IFN-γ production during xenograft rejection. [Copyright &y& Elsevier]

OBJECTIVE — The incidence of posttransplantation diabetes mellitus (PTDM) has been reported to vary according to different study populations or different definitions. In this study, using American Diabetes Association criteria, the incidence and clinical characteristics of PTDM in Korean renal allograft recipients undergoing tacrolimus-based immunosuppression were examined. RESEARCH DESIGN AND METHODS — A total of 21 patients taking tacrolimus as primary immunosuppressant were recruited and tested with a serial 75-g oral glucose tolerance test at 0, 1, 3, and 6 months after renal transplantation. RESULTS — The cumulative incidence of PTDM was 52.4% at 1 month and 57.1% at 3 and 6 months. The baseline characteristics of the PTDM group were old age (especially >40 years), a high BMI, a high fasting glucose level, a high plasma insulin level, and increased insulin resistance. Among these parameters, old age was the only independent risk factor. The insulin secretory capacity in the PTDM group was maximally suppressed 3 months after transplantation. Thereafter, it was gradually restored along with dose reduction of tacrolimus. CONCLUSIONS — Routine screening for PTDM is necessary in patients over 40 years of age who are undergoing a relatively higher dose tacrolimus therapy during the early course of postrenal transplantation. [ABSTRACT FROM AUTHOR]

The effect of the reactor configuration and several key parameters such as the gas temperature, humidity, and flow rate on the corona discharge plasma in honeycomb monoliths was investigated. The AC corona discharge-based plasma reactor consisted of two parallel electrodes (perforated disk/wire-mesh) placed at both ends of the honeycomb monolith. Although the wire-mesh electrode offers increased sharpness, the perforated disk electrode, where the corona discharge started at the sharp edges of the holes, produced more discharge power because of the larger effective electrode area. Loading a small amount of metal onto the monolith was found to increase the discharge power significantly. Coating the monolith with a zeolite such as ZSM-5 (Si/Al: 23.9) led to a decrease in the discharge power because of its hydrophobic nature and large surface area. The result also revealed that the operating temperature, the humidity of the feed gas, and the gas velocity were key factors affecting the discharge performance. The discharge power was inversely proportional to the temperature. On the other hand, the use of a high-velocity feed gas with high water vapor content was found to be particularly advantageous for obtaining high discharge power. ga1 • A honeycomb plasma reactor for practical-environmental applications. • Successful generation of large-volume air plasma in commercial monoliths. • Enhancing discharge power by metal-coating over commercial monolith. • Increase in discharge power with increasing either air flow rate or humidity. [ABSTRACT FROM AUTHOR]

Nonthermal plasma combined with a practical-scale honeycomb catalyst of 5.0 cm in height and 9.3 cm in diameter was investigated for the removal of toluene. The creation of plasma in the honeycomb catalyst greatly depended on the humidity of the feed gas and the presence of metals on the honeycomb surface. Compared to the bare ceramic honeycomb, the metal-loaded one gave higher toluene removal efficiency because the decomposition of toluene by the plasma-generated reactive species occurred not only homogeneously in the gas phase but also heterogeneously on the catalyst surface. The present plasma-catalytic reactor was able to successfully remove about 80% of dilute toluene (15 ppm in air) at a large flow rate of 60 L/min with a specific energy input of 58 J/L. The honeycomb-based plasma-catalytic reactor system is promising for practical applications since it can overcome such problems as high-pressure drop and difficulty in scale-up encountered in packed-bed reactors. ga1 • The removal of toluene investigates on a practical-scale honeycomb catalyst. • A large flow rate without significant pressure drop is used to generate plasma. • Plasma intensity largely depends on the humidity of the feed gas. • The metal clusters dotted on the honeycomb surface can act as floating grounds. [ABSTRACT FROM AUTHOR]

As one of the most abundant neurotransmitters in the brain and the spinal cord, glutamate plays many important roles in the nervous system. Precise information about the level of glutamate in the extracellular space of living brain tissue may provide new insights on fundamental understanding of the role of glutamate in neurological disorders as well as neurophysiological phenomena. Electrochemical sensor has emerged as a promising solution that can satisfy the requirement for highly reliable and continuous monitoring method with good spatiotemporal resolution for characterization of extracellular glutamate concentration. Recently, we published a method to create a simple printable glutamate biosensor using platinum nanoparticles. In this work, we introduce an even simpler and lower cost conductive polymer composite using commercially available activated carbon with platinum microparticles to easily fabricate highly sensitive glutamate biosensor using direct ink writing method. The fabricated biosensors are functionality superior than previously reported with the sensitivity of 5.73 ± 0.078 nA μM−1 mm−2, detection limit of 0.03 μM, response time less than or equal to 1 s, and a linear range from 1 μM up to 925 μM. In this study, we utilize astrocyte cell culture to demonstrate our biosensor's ability to monitor glutamate uptake process. We also demonstrate direct measurement of glutamate release from optogenetic stimulation in mouse primary visual cortex (V1) brain slices. Unlabelled Image • A low-cost composite using commercially available activated carbon-platinum microparticles was prepared. • Flexible biosensor was fabricated with high sensitivity, low detection limit, good response time and high linear range. • Printing parameters and conductive inks for direct ink writing were optimized to obtain microscale sensor. • Continuous monitoring of extracellular glutamate consumption in astrocyte cell culture was carried out. • Direct measurement of glutamate releases due to optogenetic stimulation in mouse primary visual cortex slices was performed. [ABSTRACT FROM AUTHOR]

As transcranial electrical stimulation (tES) is an emerging and promising technique for neuromodulation, we developed a novel device; wirelessly-powered, extracranial brain activator (ECBA), which is mounted subcutaneously, and its neuromodulation effect was investigated. The oscillatory changes in electrocorticography (EcoG) were analyzed from two types of stimulation. Two weeks prior to the recording experiment, we underwent surgery for implantation of subdural strips and ECBA module over centroparietal regions of anesthetized beagles. Low-frequency stimulation (LFS) and subsequent high-frequency stimulation (HFS) protocols (600 pulses respectively) were applied. Then, the power changes before and after each stimulation in five different bands were compared. A significantly larger voltage difference with subcutaneous than transcutaneous stimulation measured at EcoG channels indicated a substantial current attenuation between the skin and skull. Compared with the baseline, all subjects showed consistently decreased delta power and increased gamma power after HFS. LFS also induced a similar, but opposite, pattern of power change in four beagles. The results from this study indicate that LFS and HFS with our novel ECBA can consistently and effectively modulate neural activity of the cortex, inducing neural inhibition and facilitation functions, respectively. Future studies are necessary to further ensuring a consistent efficacy and long-term safety. [ABSTRACT FROM AUTHOR]

Front Cover: The feature describes two different types of chemical sensors, i.e., chemiresistive type sensors and optical sensors. For the chemiresistive type sensors, electrical signals are modulated during the reaction with chemical gas species. On the other hand, distinctive color changes are occurred in the case of optical sensors after the reaction with chemical analytes. The feature is designed for the review paper about one‐dimensional nanofibrous sensing structures for chemiresistive type sensors and optical sensors. This is reported by Seon‐Jin Choi, Luana Persano, Andrea Camposeo, Ji‐Soo Jang, Won‐Tae Koo, Sang‐Joon Kim, Hee‐Jin Cho, Il‐Doo Kim and Dario Pisignano, in article number 1600569. [ABSTRACT FROM AUTHOR]

Background. Hyperuricaemia commonly occurs in renal transplant recipients (RTRs), but the effects of post-transplant hyperuricaemia on kidney transplant outcome have not been clearly established. This work was designed to explore the impact of hyperuricaemia on renal transplant outcome. Methods. The authors examined this issue by analysing the clinical outcome of 281 RTRs. Hyperuricaemia (defined as UA > 7.0 mg/dl in men and >6.0 mg/dl in women for at least two consecutive tests, n = 121) was classified as early onset (within 1 year of transplant, n = 90) or late onset (n = 31). Graft function was estimated using the MDRD Study Equation 7 (eGFRMDRD). Results. As late-onset hyperuricaemia was found to be induced by a progressive decline in the graft function (P P = 0.035) and a poorer graft survival (P = 0.026) by multivariate analysis, whereas mild hyperuricaemia was not. The impact of moderate-to-severe hyperuricaemia on renal transplant survival was dependent on the duration of exposure. Likewise, the detrimental effect of early-onset hyperuricaemia on the graft function was dependent on UA levels and exposure time. After control of the baseline graft function by analysis of only recipients with a good graft function at 1 year post-transplantation (eGFRMDRD > 60 ml/min), moderate-to-severe early-onset hyperuricaemia was also found to be a marker of long-term graft dysfunction and failure. Conclusion. Moderate-to-severe early-onset hyperuri- caemia may be a prognostic marker of the long-term graft outcome in RTRs, which needs further investigation. [ABSTRACT FROM AUTHOR]