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Purpose The objective of this study was to assess the feasibility of incorporating virtual reality/augmented reality (VR/AR) programs into practical tests administered as part of the Korean Radiological Technologists Licensing Examination (KRTLE). This evaluation is grounded in a comprehensive survey that targeted enrolled students in departments of radiology across the nation. Methods In total, 682 students from radiology departments across the nation were participants in the survey. An online survey platform was used, and the questionnaire was structured into 5 distinct sections and 27 questions. A frequency analysis for each section of the survey was conducted using IBM SPSS ver. 27.0. Results Direct or indirect exposure to VR/AR content was reported by 67.7% of all respondents. Furthermore, 55.4% of the respondents expressed that VR/AR could be integrated into their classes, which signified a widespread acknowledgment of VR among the students. With regards to the integration of a VR/AR or mixed reality program into the practical tests for purposes of the KRTLE, a substantial amount of the respondents (57.3%) exhibited a positive inclination and recommended its introduction. Conclusion The application of VR/AR programs within practical tests of the KRTLE will be used as an alternative for evaluating clinical examination procedures and validating job skills.

Purpose In the coronavirus disease 2019 pandemic, it is essential to supplement the changes in visiting patterns of individual emergency departments (EDs) to determine how to allocate emergency medicine resources. We compared the clinical features of children visiting the ED before and during the pandemic. Methods Children younger than 18 years who visited the ED from February 2019 through December 2020, except January 2020, were enrolled, and divided into those who visited before and after January 2020 (the pre-pandemic and pandemic groups, respectively). We compared the 2 groups in terms of the baseline characteristics (age, sex, mode and route of arrival, cause of visit, and time of visit), chief complaint, ED diagnosis, initial acuity and its accuracy, and ED outcomes (length of stay and disposition). Results The 31,036 children were categorized into the pre-pandemic (21,027 [67.8%]) and pandemic (10,009 [32.2%]) groups with a 52.4% decrease in the number of visits to the ED in the latter group. This decrease was more prominent in age 2-5 years (from 37.3% to 33.2%; P < 0.001), fever as a chief complaint (from 27.8% to 16.5%), diagnoses related to infection or the respiratory system (from 36.8% to 14.3%) or transfer to the ED (from 8.1% to 6.4%; P < 0.001). In contrast, increases were noted in age 12-17 years (from 14.9% to 17.4%; P < 0.001), injury (from 36.5% to 52.5%; P < 0.001), visits in the evening (from 54.9% to 57.4%; P < 0.001), length of stay longer than 6 hours (from 3.5% to 6.3%; P = 0.033), and low acuity (from 97.8% to 98.2%; P = 0.031). Conclusion The pandemic has brought about changes in visiting patterns of the ED. This study may help prepare strategies for the appropriate allocation and deployment of emergency medicine resources in the pandemic era.

The 90 kDa ribosomal S6 kinases (RSKs) are serine threonine kinases comprising four isoforms. The isoforms can have overlapping functions in regulation of migration, invasion, proliferation, survival, and transcription in various cancer types. However, isoform specific differences in RSK1 versus RSK2 functions in gene regulation are not yet defined. Here, we delineate ribosomal S6 kinases isoform-specific transcriptional gene regulation by comparing transcription programs in RSK1 and RSK2 knockout cells using microarray analysis. Microarray analysis revealed significantly different mRNA expression patterns between RSK1 knockout and RSK2 knockout cell lines. Importantly some of these functions have not been previously recognized. Our analysis revealed RSK1 has specific roles in cell adhesion, cell cycle regulation and DNA replication and repair pathways, while RSK2 has specific roles in the immune response and interferon signaling pathways. We further validated that the identified gene sets significantly correlated with mRNA datasets from cancer patients. We examined the functional significance of the identified transcriptional programs using cell assays. In alignment with the microarray analysis, we found that RSK1 modulates the mRNA and protein expression of Fibronectin1, affecting cell adhesion and CDK2, affecting S-phase arrest in the cell cycle, and impairing DNA replication and repair. Under similar conditions, RSK2 showed increased ISG15 transcriptional expression, affecting the immune response pathway and cytokine expression. Collectively, our findings revealed the occurrence of RSK1 and RSK2 specific transcriptional regulation, defining separate functions of these closely related isoforms.

Objective This study aimed to clarify the relative prognostic value of each History, Electrocardiography, Age, Risk Factors, and Troponin (HEART) score component for major adverse cardiac events (MACE) within 3 months and validate the modified HEART (mHEART) score. Methods This study evaluated the HEART score components for patients with chest symptoms visiting the emergency department from November 19, 2018 to November 19, 2019. All components were evaluated using logistic regression analysis and the scores for HEART, mHEART, and Thrombolysis in Myocardial Infarction (TIMI) were determined using the receiver operating characteristics curve. Results The patients were divided into a derivation (809 patients) and a validation group (298 patients). In multivariate analysis, age did not show statistical significance in the detection of MACE within 3 months and the mHEART score was calculated after omitting the age component. The areas under the receiver operating characteristics curves for HEART, mHEART and TIMI scores in the prediction of MACE within 3 months were 0.88, 0.91, and 0.83, respectively, in the derivation group; and 0.88, 0.91, and 0.81, respectively, in the validation group. When the cutoff value for each scoring system was determined for the maintenance of a negative predictive value for a MACE rate >99%, the mHEART score showed the highest sensitivity, specificity, positive predictive value, and negative predictive value (97.4%, 54.2%, 23.7%, and 99.3%, respectively). Conclusion Our study showed that the mHEART score better detects short-term MACE in high-risk patients and ensures the safe disposition of low-risk patients than the HEART and TIMI scores.

Abstract Hematuria, either glomerular or extraglomerular, is defined as 3 or more red blood cells (RBCs)/high power field. Currently, urinalyses are commonly performed using automated urine sediment analyzers. To assess whether RBC counting by automated urine sediment analyzers is reliable for defining hematuria in glomerular disease, random specimen urinalyses of men with nephritic glomerular disease (7674 urinalyses) and bladder cancer (12,510 urinalyses) were retrospectively reviewed. Urine RBCs were counted by an automated urine sediment analyzer based on flow cytometry (UF-1000i, Sysmex Corporation) or digital image analysis (Cobas 6500, Roche Diagnostics GmbH). In about 20% of urine specimens, the specific gravity was less than 1.010, making the RBC counts unreliable. In the urine specimens with specific gravity ≥ 1.010, RBC counts measured using either UF-1000i or Cobas 6500 were well correlated with the positive grades in the dipstick blood test. However, at a trace, 1+, or higher positive dipstick tests for blood, RBC counts were graded significantly lower in glomerular disease than in bladder cancer. The findings suggest that RBC counting by UF-1000i or Cobas 6500 underestimates the severity of hematuria in glomerular disease, possibly because dysmorphic RBCs in glomerular disease are susceptible to hemolysis and/or fail to be properly recognized.

Abstract Endosomal trafficking of cell surface receptors is essential to their function. Integrins are transmembrane receptors that integrate adhesion to the extracellular matrix with engagement of the cytoskeleton. Ligated integrins mediate diverse signals that regulate matrix assembly, cell survival, cell morphology, and cell motility. Endosomal trafficking of integrins modulates these signals and contributes to cell motility and is required for cancer cell invasion. The phosphoprotein PEA-15 modulates integrin activation and ERK MAP Kinase signaling. To elucidate novel PEA-15 functions we utilized an unbiased proteomics approach. We identified several binding partners for PEA-15 in the endosome including clathrin and AP-2 as well as integrin β1 and other focal adhesion complex proteins. We confirmed these interactions using proximity ligation analysis, immunofluorescence imaging, pull-down and co-immunoprecipitation. We further found that PEA-15 is enriched in endosomes and was required for efficient endosomal internalization of α5β1 integrin and cellular migration. Importantly, PEA-15 promotion of migration was dependent on PEA-15 phosphorylation at serines 104 and 116. These data support a novel endosomal role for PEA-15 in control of endosomal trafficking of integrins through an association with the β1 integrin and clathrin complexes, and thereby regulation of cell motility.

Objective Recent studies have suggested that deep-learning models can satisfactorily assist in fracture diagnosis. We aimed to evaluate the performance of two of such models in wrist fracture detection. Methods We collected image data of patients who visited with wrist trauma at the emergency department. A dataset extracted from January 2018 to May 2020 was split into training (90%) and test (10%) datasets, and two types of convolutional neural networks (i.e., DenseNet-161 and ResNet-152) were trained to detect wrist fractures. Gradient-weighted class activation mapping was used to highlight the regions of radiograph scans that contributed to the decision of the model. Performance of the convolutional neural network models was evaluated using the area under the receiver operating characteristic curve. Results For model training, we used 4,551 radiographs from 798 patients and 4,443 radiographs from 1,481 patients with and without fractures, respectively. The remaining 10% (300 radiographs from 100 patients with fractures and 690 radiographs from 230 patients without fractures) was used as a test dataset. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DenseNet-161 and ResNet-152 in the test dataset were 90.3%, 90.3%, 80.3%, 95.6%, and 90.3% and 88.6%, 88.4%, 76.9%, 94.7%, and 88.5%, respectively. The area under the receiver operating characteristic curves of DenseNet-161 and ResNet-152 for wrist fracture detection were 0.962 and 0.947, respectively. Conclusion We demonstrated that DenseNet-161 and ResNet-152 models could help detect wrist fractures in the emergency room with satisfactory performance.

Background Glycosuria is one of the manifestations of acute tubulointerstitial nephritis (ATIN), but may also be observed in other renal diseases. In this study, we investigated the value of non-diabetic glycosuria as a diagnostic clue for ATIN. Methods We retrospectively reviewed the medical records of adult patients who underwent a kidney biopsy as an evaluation for serum creatinine > 1.4 mg/dL. Patients with proteinuria in the nephrotic range, diabetes mellitus, or transplanted kidney were excluded. The laboratory abnormalities suggestive of tubular injury were compared between 28 patients (14 men and 14 women, mean age 48.5 ± 14.1 years) with ATIN and 116 patients (76 men and 40 women, mean age 53.1 ± 15.0 years) with other diagnoses. Results In ATIN, glycosuria (≥ 1+ on dipstick; 68%) was more frequent than hypophosphatemia (18%), hypouricemia (18%), hypokalemia (18%), and tubular proteinuria (40%). In other diagnoses, glycosuria (≥ 1+) was detected in 7 (6%) patients; 6 of them had the histological diagnosis of antineutrophil cytoplasmic antibody-associated glomerulonephritis. The presence of glycosuria (≥ 1+) had 68% sensitivity and 94% specificity for ATIN, with the positive likelihood ratio of 11.24 and the negative likelihood ratio of 0.34. Pyuria and low total CO2 were equally and more sensitive (68% and 71%, respectively) than glycosuria (≥ 1+), but had no diagnostic value due to low specificities (58% and 60%, respectively). Conclusion In non-diabetic, non-nephrotic patients undergoing a kidney biopsy for azotemia, 1+ or higher glycosuria, if present, was a good predictor of the diagnosis of ATIN.

Abstract Background Short-term hemoglobin (Hb) variability related to volume status is observed in chronic kidney disease (CKD) patients receiving hemodialysis (HD). Given the lack of studies regarding outcomes according to the day of Hb sampling, the existing guidelines do not strongly recommend regarding measurement timing. Pre-dialysis mid-week sampling (Wednesday and Thursday) is preferable to minimize short-term Hb variability, although numerous HD centers perform early-week sampling (Monday and Tuesday). The different measurement days may influence the prescribed dose of erythropoiesis-stimulating agent (ESA) and related patient outcomes. We investigated changes in Hb levels and ESA doses according to the Hb measurement day among HD patients. Methods Starting September 2013, the day for pre-dialysis Hb measurement at the Asan Medical Center was changed from early-week days to mid-week days. This single-center retrospective study evaluated medical records of 92 patients who received maintenance HD between September 2012 and August 2014. Results There was no significant difference in the mean Hb levels between early-week days and mid-week days (10.71 ± 0.06 g/dL vs. 10.78 ± 0.47 g/dL, p = 0.105). However, the mean doses of darbepoetin-α on early-week days were higher than those on mid-week days (175.4 ± 72.5 μg/month vs. 163.7 ± 83.6 μg/month, p = 0.022). The mean doses of intravenous iron hydroxide sucrose for early-week measurements were also higher than those for mid-week measurements (623.0 ± 489.0 mg/year vs. 447.0 ± 505.2 mg/year, p = 0.001). The mean interdialytic weight gains were 2.81 ± 0.82 kg on early-week days and 1.99 ± 0.61 kg on mid-week days (p

Ras mutations are present in only a subset of sporadic human cutaneous squamous cell carcinomas (cSCC) even though Ras is activated in most. This suggests that other mechanisms of Ras activation play a role in the disease. The aberrant expression of RasGRP1, a guanyl nucleotide exchange factor for Ras, is critical for mouse cSCC development through its ability to increase Ras activity. However, the role of RasGRP1 in human keratinocyte carcinogenesis remains unknown. Here we report that RasGRP1 is significantly elevated in human cSCC and that high RasGRP1 expression in human primary keratinocytes triggered activation of endogenous Ras and significant morphological changes including cytoplasmic vacuole formation and growth arrest. Moreover, RasGRP1-expressing cells were autophagic as indicated by LC3-II increase and the formation of LC3 punctae. In an in vitro organotypic skin model, wild type keratinocytes generated a well-stratified epithelium, while RasGRP1-expressing cells failed to do so. Finally, RasGRP1 induced transformation-like changes in skin cells from Li-Fraumeni patients with inactivating p53 mutations, demonstrating the oncogenic potential of this protein. These results support a role for RasGRP1 in human epidermal keratinocyte carcinogenesis and might serve as an important new therapeutic target.

Background/Aims: High-mobility group box 1 (HMGB1) elicits inflammatory responses through interactions with the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). We investigated how RAGE and TLR4 expressions are regulated after HMGB1 stimulation in cultured human aortic endothelial cells (HAECs). Methods: RAGE and TLR4 expressions were analyzed by Western blot analysis and immunofluorescence staining. A disintegrin and metalloprotease 17 (ADAM17) activity was measured using a fluorogenic substrate. Results: Upon treatment with HMGB1, both RAGE and TLR4 began to decrease in cell lysate and remained decreased up to 24 h. The decrease in cellular RAGE and TLR4 was accompanied by an increase of N-terminal fragment of RAGE and TLR4 in culture supernatant, indicating ectodomain shedding of the receptors. HMGB1 activated p38 mitogen-activated protein kinase (p38 MAPK) and ADAM17, while HMGB1-induced ADAM17 activation was inhibited by SB203580, a p38 MAPK inhibitor. HMGB1-induced ectodomain shedding of RAGE and TLR4 was prevented by siRNA depletion of ADAM17 as well as TAPI-2, an inhibitor of ADAM family, and SB203580. HMGB1 pretreatment abolished p38 MAPK activation in response to 2nd HMGB1 stimulation. In the cells depleted of ADAM17, HMGB1-induced p38 MAPK activation was prolonged. siRNA depletion of RAGE, but not TLR4, suppressed HMGB1-induced p38 MAPK activation. Conclusion: In response to HMGB1 stimulation, HAECs rapidly undergo ectodomain shedding of RAGE and TLR4, and thereby become insensitive to further HMGB1 stimulation. ADAM17, activated through RAGE-p38 MAPK pathway, is implicated in the ectodomain cleavage of the receptors.

Intradialytic hypotension during dialysis adversely affects a patient's prognosis and increases mortality. We report a case in which intradialytic hypotension that persisted after the administration of midodrine was relieved after the use of fludrocortisone. Administration of 0.2 mg of fludrocortisone occurred 30 minutes before dialysis. We compared 45 sessions of dialysis without fludrocortisone administration and 45 sessions of dialysis with fludrocortisone administration in one patient. The number of times in which systolic blood pressure became lower than 80 mmHg and the number of early terminations of dialysis due to a decrease in systolic blood pressure were higher in the sessions without fludrocortisone administration than in the sessions with fludrocortisone administration (P < 0.05). Fludrocortisone may be helpful for the treatment of intradialytic hypotension that does not respond to midodrine administration.

Background/Aims: Lipopolysaccharide (LPS)-activated monocytes/macrophages develop endotoxin tolerance in part by reducing cell surface toll-like receptor 4 (TLR4) through cluster of differentiation 14 (CD14)-dependent endocytosis. In case of endothelial cells, CD14 is expressed in low copy numbers as compared with monocytes/macrophages. Thus, we explored how endothelial cells regulate TLR4 expression after LPS stimulation. Methods: Cultured human aortic endothelial cells (HAECs) were treated with LPS. TLR4 expression was analyzed by Western blot analysis and immunofluorescence staining. A disintegrin and metalloprotease 17 (ADAM17) activity was measured using a fluorescent substrate. Results: TLR4 in cell lysate began to decrease within 30 min of LPS treatment with a maximal reduction at 2 h, and it was accompanied by an increase of N-terminal fragment of TLR4 in culture supernatant, indicating ectodomain shedding of the receptor. LPS activated p38 mitogen-activated protein kinase (p38 MAPK) and ADAM17, while LPS-induced ADAM17 activation was inhibited by SB203580, a p38 MAPK inhibitor. LPS-induced ectodomain shedding of TLR4 was attenuated by siRNA depletion of ADAM17 as well as TAPI-2 (an inhibitor of ADAM family) and SB203580. LPS pretreatment resulted in a blunted response of p38 MAPK activation to further LPS stimulation. In the cells depleted of ADAM17, LPS-induced p38 MAPK activation was prolonged and LPS-induced intercellular adhesion molecule-1 expression was potentiated. Conclusion: HAECs respond to LPS by rapid shedding of the ectodomain of TLR4 and thereby reduce the responsiveness to subsequent LPS exposure. ADAM17, downstream of p38 MAPK, is implicated in the ectodomain cleavage of TLR4.

Background/Aims: We investigated how diosgenin, a steroidal sapogenin, has anti-tumor necrosis factor-α (TNF-α) effects in human aortic endothelial cells (HAECs). Methods: Tumor necrosis factor receptor 1 (TNFR1) was assessed by Western blot analysis. Intracellular Ca2+ was measured using Fluo-4 AM. Immunofluorescence staining was performed for a disintegrin and metalloprotease 10 (ADAM10). Results: Diosgenin (1 ∼ 100 nM) induced ectodomain shedding of TNFR1 within 30 min and attenuated TNF-α-induced intercellular adhesion molecule-1 (ICAM-1) expression. Upon treatment with diosgenin, extracellular Ca2+ entered into the cells via L-type calcium channels, whereas diosgenin-induced ectodomain shedding of TNFR1 was almost completely inhibited by BAPTA-AM (intracellular Ca2+ chelator), verapamil (L-type calcium channel antagonist) and the absence of extracellular Ca2+. Diosgenin caused translocation of ADAM10 to the cell surface, which was mediated by extracellular Ca2+ influx. Depletion of ADAM10 prevented diosgenin-induced ectodomain shedding of TNFR1 and abolished the inhibitory effect of diosgenin on TNF-α-induced ICAM-1 expression. Diosgenin did not induce extracellular Ca2+ influx and ectodomain shedding of TNFR1 in cells depleted of 1,25D3-membrane associated rapid response steroid-binding receptor (1,25D3-MARRS receptor/ERp57). Conclusion: Diosgenin elicits L-type calcium channel-mediated extracellular Ca2+ influx, and thereby induces ADAM10-mediated ectodomain shedding of TNFR1. This effect of diosgenin was exerted through 1,25D3-MARRS receptor/ERp57.

Background/Aims: We investigated how 1,25-dihydroxyvitamin D3 (1,25D3) inhibits the effects of lipopolysaccharide (LPS) in human aortic endothelial cells. Methods: Cellular signaling was explored by determination of protein abundance with Western blot, measurement of cytosolic Ca2+ concentration and immunofluorescence staining for a disintegrin and metalloprotease 10 (ADAM10). Results: LPS stimulated the expression of intercellular adhesion molecule 1 (ICAM-1) through toll-like receptor 4 (TLR4) and subsequent activation of p38 mitogen-activated protein kinase (p38 MAPK). Pretreatment with 1,25D3 attenuated LPS-induced p38 MAPK activation and ICAM-1 expression by causing ectodomain shedding of TLR4. This effect of 1,25D3 depended on its ability to induce a rapid extracellular Ca2+ influx through L-type calcium channels because the ectodomain shedding was prevented by the absence of extracellular Ca2+ or the presence of verapamil. TLR4 ectodomain shedding was also induced by Bay K8644 (L-type calcium channel agonist). Both 1,25D3 and Bay K8644 caused extracellular Ca2+ influx-dependent ADAM10 translocation to the cell surface. Depletion of ADAM10 by siRNA transfection prevented 1,25D3- and Bay K8644-induced ectodomain shedding of TLR4, and abolished the inhibitory effect of 1,25D3 on LPS-induced ICAM-1 expression. Conclusion: 1,25D3 causes ectodomain shedding of TLR4 and thereby decreases the responsiveness of cells to LPS. ADAM10, activated by extracellular Ca2+ influx, was implicated in the ectodomain cleavage of TLR4.

Background/Aims: Toll-like receptor 4 (TLR4) interacts with endogenous substances as well as lipopolysaccharide. We explored whether TLR4 is implicated in tumor necrosis factor-α (TNF-α) signal transduction in human aortic endothelial cells. Methods: The pathway was evaluated by transfection of siRNAs, immunoprecipitation and Western blot analysis. Results: TNF-α activated spleen tyrosine kinase (Syk) within 10 min, which led to endothelin-1 (ET-1) production. TLR4 was also rapidly activated by TNF-α stimulation, as shown by recruitment of interleukin-1 receptor-associated kinase 1 to TLR4 and its adaptor molecule, myeloid differentiation factor 88 (MyD88). siRNA depletion of TLR4 markedly attenuated TNF-α-induced Syk activation and ET-1 production. TLR4 inhibitor (CLI-095), TLR4-neutralizing antibody and siRNA depletion of MyD88 also attenuated TNF-α-induced Syk activation. Syk was co-immunoprecipitated with TLR4, and TNF-α activated Syk bound to TLR4. High-mobility group box 1 (HMGB1) was rapidly released and associated with TLR4 after TNF-α stimulation with a peak at 5 min, which was prevented by N-acetylcysteine, an antioxidant. Glycyrrhizin (HMGB1 inhibitor), HMGB1-neutralizing antibody and siRNA depletion of HMGB1 all suppressed TNF-α-induced Syk activation and ET-1 production. Conclusion: Upon TNF-α stimulation, TLR4 is activated by HMGB1 that is immediately released after the generation of reactive oxygen species, and plays a crucial role in the signal transduction.

Background/Aims: We investigated the mechanism underlying anti-tumor necrosis factor-α (TNF-α) effects of epigallocatechin-3-gallate (EGCG) in human aortic endothelial cells. Methods: Tumor necrosis factor receptor 1 (TNFR1) was assessed by Western blot analysis. Cytosolic Ca2+ was measured using Fluo-4 AM. A disintegrin and metalloprotease 10 (ADAM10) was localized by immunofluorescence staining. Results: EGCG caused ectodomain shedding of TNFR1 within 30 min and attenuated TNF-α-induced endothelin-1 (ET-1) expression. EGCG-induced TNFR1 ectodomain shedding was prevented by BAPTA-AM (intracellular Ca2+ chelator), but not by the absence of extracellular Ca2+. In physiologic extracellular Ca2+ concentration, EGCG markedly increased cytosolic Ca2+. Even in the absence of extracellular Ca2+, EGCG raised cytosolic Ca2+, though less potently. siRNA depletion of ADAM10 prevented EGCG-induced ectodomain shedding of TNFR1 and also diminished the inhibitory effect of EGCG on TNF-α-induced ET-1 expression. EGCG caused translocation of ADAM10 to the plasma membrane, and this effect was prevented by BAPTA-AM. Besides extracellular Ca2+ influx, release of intracellular stored Ca2+ caused ADAM10-dependent ectodomain shedding of TNFR1. Conclusion: EGCG decreases the responsiveness of cells to TNF-α by causing ADAM10-dependent ectodomain shedding of TNFR1. This effect was attributed to its property to increase cytosolic Ca2+ through both extracellular Ca2+ influx and release of stored Ca2+.

Background/Aims: High glucose activates spleen tyrosine kinase (Syk) in human proximal tubular epithelial cells (HK-2 cells), which leads to NF-κB activation and transforming growth factor-ß1 (TGF-ß1) production. We explored the signal transduction pathway from high glucose to Syk activation. Methods: The pathway was evaluated by siRNA transfection, immunoprecipitation and Western blot. Results: High glucose stimulated Syk activation within 10 min. Depletion of toll-like receptor 4 (TLR4) attenuated high glucose-induced Syk activation, NF-κB p65 nuclear translocation, and TGF-ß1 production. In addition, TLR4 inhibitor (CLI-095), TLR4-neutralizing antibody, and depletion of myeloid differentiation factor 88 (MyD88) all attenuated high glucose-induced Syk activation. As an evidence of TLR4 activation, interleukin-1 receptor-associated kinase 1 was recruited to MyD88 and TLR4 upon exposure to high glucose. Syk was co-immunoprecipitated with TLR4, and Syk bound to TLR4 was activated by high glucose. High-mobility group box-1 (HMGB-1), an endogenous activator of TLR4, rapidly increased in TLR4 immunoprecipitates upon high glucose stimulation, and this association was reduced by N-acetylcysteine, an antioxidant. An HMGB-1 inhibitor glycyrrhizin suppressed high glucose-induced Syk activation. Conclusion: Syk is constitutively associated with TLR4. High glucose induces an immediate, reactive oxygen species-dependent, extracellular release of HMGB-1 which binds to TLR4 and activates it, leading to Syk activation.

ZBTB4 is a transcriptional repressor and examination of publically-available microarray data sets demonstrated an inverse relationship in the prognostic value and expression of ZBTB4 and the histone methyltransferase EZH2 in tumors from breast cancer patients. The possibility of functional interactions between EZH2 and ZBTB4 was investigated in breast cancer cells and the results showed that EZH2 is directly suppressed by ZBTB4 which in turn is regulated (suppressed) by miR-106b and other paralogues from the miR-17-92, miR-106b-25 and miR-106a-363 clusters that are highly expressed in breast and other tumors. ZBTB4 also acts a suppressor of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4, and RNA interference studies show that Sp proteins are required for EZH2 expression. The prediction analysis results from breast cancer patient array data sets confirm an association of Sp1-dependent EZH2 gene signature with decreased survival of breast cancer patients. Disruption of oncogenic miR-ZBTB4 signaling axis by anticancer agent such as betulinic acid that induce down-regulation of Sp proteins in breast cancer cells resulted in inhibition of tumor growth and colonization of breast cancer cells in a mouse model. Thus, EZH2 is reciprocally regulated by a novel signaling network consisting of Sp proteins, oncogenic miRs and ZBTB4, and modulation of this gene network is a novel therapeutic approach for treatment of breast cancer and possibly other cancers.

Endoplasmic reticulum (ER) stress is increasingly identified as modulator of fibrosis. Losartan, an angiotensin II receptor blocker, has been widely used as the first choice of treatment in chronic renal diseases. We postulated that anti-fibrotic effect of losartan is mediated through inhibition of ER stress via SIRT1 (silent mating type information regulation 2 homolog 1) hemeoxygenase-1 (HO-1)/thioredoxin pathway. Renal tubular cells, tunicamycin (TM)-induced ER stress, and unilateral ureteral obstruction (UUO) mouse model were used. Expression of ER stress was assessed by Western blot analysis and immunohistochemical stain. ER stress was induced by chemical ER stress inducer, tunicamycin, and non-chemical inducers such as TGF-β, angiotensin II, high glucose, and albumin. Losartan suppressed the TM-induced ER stress, as shown by inhibition of TM-induced expression of GRP78 (glucose related protein 78) and p-eIF2α (phosphospecific-eukaryotic translation initiation factor-2α), through up-regulation of SIRT1 via HO-1 and thioredoxin. Losartan also suppressed the ER stress by non-chemical inducers. In both animal models, losartan reduced the tubular expression of GRP78, which were abolished by pretreatment with sirtinol (SIRT1 inhibitor). Sirtinol also blocked the inhibitory effect of losartan on the UUO-induced renal fibrosis. These findings provide new insights into renoprotective effects of losartan and suggest that SIRT1, HO-1, and thioredoxin may be potential pharmacological targets in kidney diseases under excessive ER stress condition.

Directed migration is essential for cell motility in many processes, including development and cancer cell invasion. RSKs (p90 ribosomal S6 kinases) have emerged as central regulators of cell migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood. We have identified a unique signaling mechanism by which RSK2 promotes cell motility through leukemia-associated RhoGEF (LARG)-dependent Rho GTPase activation. RSK2 directly interacts with LARG and nucleotide-bound Rho isoforms, but not Rac1 or Cdc42. We further show that epidermal growth factor or FBS stimulation induces association of endogenous RSK2 with LARG and LARG with RhoA. In response to these stimuli, RSK2 phosphorylates LARG at Ser1288 and thereby activates RhoA. Phosphorylation of RSK2 at threonine 577 is essential for activation of LARG-RhoA. Moreover, RSK2-mediated motility signaling depends on RhoA and -B, but not RhoC. These results establish a unique RSK2-dependent LARG-RhoA signaling module as a central organizer of directed cell migration and invasion. [ABSTRACT FROM AUTHOR]

Background/Aims: We investigated how 1,25-dihydroxyvitamin D3 (1,25D3) inhibits the effects of lipopolysaccharide (LPS) in human aortic endothelial cells. Methods: Cellular signaling was explored by determination of protein abundance with Western blot, measurement of cytosolic Ca2+ concentration and immunofluorescence staining for a disintegrin and metalloprotease 10 (ADAM10). Results: LPS stimulated the expression of intercellular adhesion molecule 1 (ICAM-1) through toll-like receptor 4 (TLR4) and subsequent activation of p38 mitogen- activated protein kinase (p38 MAPK). Pretreatment with 1,25D3 attenuated LPS-induced p38 MAPK activation and ICAM-1 expression by causing ectodomain shedding of TLR4. This effect of 1,25D3 depended on its ability to induce a rapid extracellular Ca2+ influx through L-type calcium channels because the ectodomain shedding was prevented by the absence of extracellular Ca2+ or the presence of verapamil. TLR4 ectodomain shedding was also induced by Bay K8644 (L-type calcium channel agonist). Both 1,25D3 and Bay K8644 caused extracellular Ca2+ influx-dependent ADAM10 translocation to the cell surface. Depletion of ADAM10 by siRNA transfection prevented 1,25D3- and Bay K8644-induced ectodomain shedding of TLR4, and abolished the inhibitory effect of 1,25D3 on LPS-induced ICAM-1 expression. Conclusion: 1,25D3 causes ectodomain shedding of TLR4 and thereby decreases the responsiveness of cells to LPS. ADAM10, activated by extracellular Ca2+ influx, was implicated in the ectodomain cleavage of TLR4. [ABSTRACT FROM AUTHOR]

Background: Rituximab is widely used in kidney transplantation. However, it is not clear whether the conventional doses of maintenance immunosuppressant in rituximab-treated kidney transplantation (KT) are appropriate. In our previous study, decreasing mycophenolate mofetil (MMF) dose due to infection did not increase the incidence of rejection or graft failure. Based on these experiences, we developed a new protocol with a lower dose of MMF and studied its clinical outcomes in rituximab-treated KT.Methods: We enrolled all patients who underwent ABO-incompatible or human leukocyte antigen (HLA)-sensitized living donor KT with the new immunosuppressant protocol after preconditioning with rituximab, but without splenectomy from November 2011 to May 2013. Seventy-two patients (group 1) were consecutively enrolled in this study and followed until November 2013. Patients from our previous study served as control groups. Sixty-seven patients received KT using rituximab with a conventional dose of MMF (group 2), and 87 patients received ABO compatible KT without need for rituximab (group 3). Clinical outcomes, including rejection, infection, and graft survival, were compared between the groups. The χ (2) test and Fisher's exact test were used for categorical variables, the Student's t-test and Mann-Whitney U test were used for continuous variables, and a log-rank test was used for mortality analysis.Results: Doses of postoperative MMF (g/day) were lower in group 1 than in the other groups (1.03 ± 0.19, 1.48 ± 0.34 and 1.48 ± 0.32 g/day at 1 week, p < 0.001). Infectious complications occurred more often in groups with conventional MMF doses (group 2 and 3) than in group 1 (16.7 vs. 37.3 %, p = 0.007 and 16.7 vs. 34.5 %, p = 0.012, respectively). Notably, group 1 showed a lower incidence of cytomegalovirus infection than group 2. However, reduction in MMF dose did not increase the incidence of acute rejection (4.2, 4.5 and 10.3 %). Only one graft failure occurred in group 2 due to vessel kinking after operation. There were no significant differences in the incidence of malignancy and mortality between groups.Conclusions: A low MMF dose reduces infection without increasing rejection or graft loss and it may be appropriate to reduce the dose of MMF for rituximab-treated KT patients. [ABSTRACT FROM AUTHOR]

After the enforcement of Waste Management Law in Korea from 1987, a systematic waste management has been made. Since then major effective policies and strategies by the government were utilized to promote reduction and recycling of waste and to implement appropriate technologies for disposing waste in safe and permanent methods. In recent the waste becomes not a waste being disposed of but resources having values, so management policy is focusing on 'waste to energy' as one of renewable energy resources and the establishment of 'sustainable and recirculating society'. By such practices for last 30 years in South Korea, the recycling rate has increased from under 10% to 80%, and the share of landfill became less than 10% in overall waste streams. Using the WARM code developed by US EPA, the greenhouse gas emissions by different practices of waste treatment were estimated for 30 years. Due to a significant increase of recycling rate, the reduction of greenhouse gas emission was achieved around 110,000 tons of CO2, from around 25,000 tons of generation to 85,000 tons of credit. The paper will present such changes in different waste streams by effective waste management efforts for last 30 years. [ABSTRACT FROM AUTHOR]

Background: Serum phosphorus concentrations are associated with an increased risk of cardiovascular disease (CVD) and mortality in patients with renal insufficiency. This association has also been reported in Western individuals without chronic kidney disease (CKD). Objective: It is unclear, however, whether this correlation occurs in Korean individuals without CKD, who usually ingest less phosphorus than do Western individuals. Design: We reviewed the findings in 402 healthy Korean adults with a mean (±SD) age of 50.8 ± 8.5 y (n = 257 men and 145 women) and a glomerular filtration rate of 83.5 ± 14.1 mL/min, who underwent health screening with electron-beam computed tomography (EBCT). The study population was separated into 4 groups on the basis of the coronary calcium concentration (Agatston score: 0, >0 to ≤10, >10 to ≤100, and >100). Mean serum phosphorus concentrations, measured ≥10 y before EBCT, were compared. Results: Multivariate analysis showed that age (P = 0.001), male sex (P = 0.002), family history of CVD (P = 0.006), serum glucose (P = 0.003), and serum phosphorus >3.6 mg/dL (P = 0.008) were significant factors influencing the coronary calcification group with an Agatston score >100, when those with an Agatston score of 0 were considered as the reference group. Compared with the group with a serum phosphorus concentration ≤3.3 mg/dL, the OR of an Agatston score >100 in individuals with a serum phosphorus concentration >3.6 to ≤3.9 mg/dL was 3.89 (95% CI: 1.43, 10.63; P = 0.008) and in those with a serum phosphorus concentration >3.9 mg/dL was 3.17 (95% CI: 1.19, 8.41; P = 0.021). Conclusion: A lower concentration of serum phosphorus within the normal range could be associated with less calcification of the coronary artery in Koreans with normal renal function. [ABSTRACT FROM AUTHOR]

Background: Many studies have been performed in kidney transplant recipients to test whether hyperuricemia plays a role in decreased kidney function, but the results have been controversial. We conducted a retrospective cohort study to assess the predictors of hyperuricemia and how uric acid (UA) influences glomerular filtration rate (GFR) changes. Methods: 556 patients who underwent kidney transplantation between January 1, 1990 and February 24, 2009, were included. Serum UA levels were routinely recorded every 3 months after transplantation. Hyperuricemia was defined as serum UA ≥6.0 mg/dl for women, and ≥7.0 mg/dl for men. A time-dependent covariate Cox model was used to assess the association of serial changes of estimated GFR (eGFR) and UA. Results: Multivariate analysis indicated that male gender, eGFR, and transplant duration were associated with higher mean UA levels. A time-dependent covariate Cox model indicated that initial eGFR level (hazard ratio: 1.001; p = 0.035) and previous UA level (hazard ratio: 1.454; p < 0.001) affected the subsequent eGFR level. Conclusions: Our results indicated a predictive relationship between UA and eGFR based on the results of a time-dependent covariate Cox model that elevated serum UA precedes a graft dysfunction in kidney transplant recipients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The epithelial-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress induced by urinary protein, particularly albumin, play an important role in tubulointerstitial injury. However, signaling pathways regulating both albumin-induced EMT and ER stress are not precisely known. We postulated that reactive oxygen species (ROS), c-Src kinase, and mammalian target of rapamysin (mTOR) would act as upstream signaling molecules. We further examined the effect of imatinib mesylate on these processes. All experiments were performed using HK-2 cells, a human proximal tubular cell line. Protein and mRNA expression were measured by Western blot analysis and real-time PCR, respectively. Exposure of tubular cells to albumin (5 mg/ml) for up to 5 days induced EMT in a time-dependent manner, as shown by conversion to the spindle-like morphology, loss of E-cadherin protein, and upregulation of α-smooth muscle actin mRNA and protein. Albumin also induced ER stress as evidenced by phosphorylation of eukaryotic translation initiation factor-2α and increased expression of GRP78 mRNA and protein. Albumin induced ROS, c-Src kinase, and mTOR as well. Antioxidants, c-Src kinase inhibitor (PP2), and mTOR inhibitor (rapamycin) suppressed the albumin-induced EMT and ER stress. Antioxidants and PP2 inhibited the albumin-induced c-Src kinase and mTOR, respectively. Imatinib suppressed the albumin-induced EMT and ER stress via inhibition of ROS and c-Src kinase. Imatinib also inhibited the albumin-induced mRNA expression of MCP-1, VCAM-1, transforming growth factor (TGF)-β1, and collagen I (α1). In conclusion, the ROS-c-Src kinase-mTOR pathway played a central role in the signaling pathway that linked albumin to EMT and ER stress. Imatinib might be beneficial in attenuating the albumin-induced tubular injury. [ABSTRACT FROM AUTHOR]

Background: Arterial blood gas analysis (ABGA) is a useful test that estimates the acid-base status of patients. However, numerically reported test results make rapid interpretation difficult. To overcome this problem, we have developed an algorithm that automatically interprets ABGA results, and assessed the validity of this algorithm for applications in clinical laboratory services. Methods: The algorithm was developed based on well-established guidelines using three test results (pH, PaCO2 and [HCO3 2]) as variables. Ninety-nine ABGA test results were analysed by the algorithm. The algorithm's interpretations and the interpretations of two representative web-based ABGA interpretation programs were compared with those of two experienced clinicians. Results: The concordance rates between the interpretations of each of the two clinicians and the algorithm were 91.9% and 97.0%, respectively. The web-based programs could not issue definitive interpretations in 15.2% and 25.3% of cases, respectively, but the algorithm issued definitive interpretations in all cases. Of the 10 cases that invoked disagreement among interpretations by the algorithm and the two clinicians, half were interpreted as compensated acid-base disorders by the algorithm but were assessed as normal by at least one of the two clinicians. In no case did the algorithm indicate a normal condition that the clinicians assessed as an abnormal condition. Conclusions: The interpretations of the algorithm showed a higher concordance rate with those of experienced clinicians than did two web-based programs. The algorithm sensitively detected acid-base disorders. The algorithm may be adopted by the clinical laboratory services to provide rapid and definitive interpretations of test results. [ABSTRACT FROM AUTHOR]

Background: Many studies have been performed in kidney transplant recipients to test whether hyperuricemia plays a role in decreased kidney function, but the results have been controversial. We conducted a retrospective cohort study to assess the predictors of hyperuricemia and how uric acid (UA) influences glomerular filtration rate (GFR) changes. Methods: 556 patients who underwent kidney transplantation between January 1, 1990 and February 24, 2009, were included. Serum UA levels were routinely recorded every 3 months after transplantation. Hyperuricemia was defined as serum UA ≥6.0 mg/dl for women, and ≥7.0 mg/dl for men. A time-dependent covariate Cox model was used to assess the association of serial changes of estimated GFR (eGFR) and UA. Results: Multivariate analysis indicated that male gender, eGFR, and transplant duration were associated with higher mean UA levels. A time-dependent covariate Cox model indicated that initial eGFR level (hazard ratio: 1.001; p = 0.035) and previous UA level (hazard ratio: 1.454; p < 0.001) affected the subsequent eGFR level. Conclusions: Our results indicated a predictive relationship between UA and eGFR based on the results of a time-dependent covariate Cox model that elevated serum UA precedes a graft dysfunction in kidney transplant recipients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The occurrence of disasters to a queueing system causes all customers to be removed if any are present. Although there has been much research on continuous-time queues with disasters, the discrete-time Geo/Geo/1 queue with disasters has appeared in the literature only recently. We extend this Geo/Geo/1 queue to the GI/Geo/1 queue. We present the probability generating function of the stationary queue length and sojourn time for the GI/Geo/1 queue. In addition, we convert our results into the Geo/Geo/1 queue and the GI/M/1 queue. [ABSTRACT FROM AUTHOR]

Aim: i.v. iron therapy is more effective in maintaining adequate iron status in haemodialysis (HD) patients than oral iron therapy (OIT). However, data on lower doses of i.v. iron therapy are insufficient. Methods: A non-randomized, open-label study was performed to compare the efficacy of low-dose (≤50 mg/week of iron sucrose) i.v. iron therapy (LD-IVIT) with OIT in HD patients with 100–800 µg/L serum ferritin levels over 4 months. Results: Eighty-nine patients in the LD-IVIT group (40 men, 49 women; aged 61 ± 13 years) and 30 patients in the oral iron therapy group (17 men, 13 women; aged 59 ± 7 years) were evaluated. After 4 months of each treatment, serum ferritin levels increased from 398 ± 137 to 529 ± 234 µg/L in the LD-IVIT group ( P < 0.01) but decreased from 351 ± 190 to 294 ± 175 µg/L in the OIT group ( P < 0.01). In the LD-IVIT group, transferrin saturation (from 28% ± 11% to 30% ± 14%, P = 0.49), weekly doses of recombinant human erythropoietin (from 5822 ± 2354 to 5636 ± 2306 IU/week, P = 0.48) and haemoglobin (from 101 ± 9 to 103 ± 9 g/L, P = 0.15) levels remained stable. Conclusion: LD-IVIT may be one of the regimens that may be considered for maintaining iron status in HD patients. However, efficacy of LD-IVIT should be verified by further randomized study. [ABSTRACT FROM AUTHOR]

Activation of nuclear factor-KB (NF-KB) occurs by dissociation from 1KB after serine or tyrosine phosphorylation of IKBU, but the way of NF-KB activation by high glucose has not been defined. High glucose is known to activate NF-KB via protein kinase C and reactive oxygen species (ROS). In this study, we investigated how high glucose activates NF-KB for CC chemokine ligand 2 production in cultured human glomerular endothelial cells. High glucose increased nuclear translocation of p65 and also increased NF-KB DNA binding activity. High glucose-induced NF-KB activation occurred without degradation of IKBα. In agreement with this, there was no increase in serine phosphorylation of IKBα, while tyrosine phosphorylation of IKBα was increased by high glucose. High glucose increased the generation of ROS, whereas both α-lipoic acid and N-acetylcysteine scavenged the ROS and decreased high glucose-induced tyrosine phosphorylation of IKBα, nuclear translocation of p65, and NF-KB DNA binding activity. Protein kinase C pseudosubstrate inhibited high glucose-induced ROS production, tyrosine phosphorylation of IKBα, and nuclear translocation of p65. Both BAY 61-3606, a specific inhibitor of Syk protein-tyrosine kinase, and small interfering RNA directed against Syk inhibited high glucose-induced tyrosine phosphorylation of lKBα as well as p65 nuclear translocation. High glucose increased tyrosine phosphorylation of Syk, while it was inhibited by α-lipoic acid and protein kinase C pseudosubstrate. In summary, high glucose-induced NF-KB activation occurred not by serine phosphorylation of IKBa. Our data suggest that ROS-mediated tyrosine phosphorylation of IKBα is the mechanism for high glucose-induced NP-KB activation, and Syk may play a role in tyrosine phosphorylation of IKBα. [ABSTRACT FROM AUTHOR]

Background: Although several previous studies have reported that kidney donors are not at increased risk for adverse effects, some donors have been found to progress to chronic kidney disease (CKD). We retrospectively evaluated the risk factors for estimated glomerular filtration rate (GFR) from abbreviated Modification of Diet in Renal Disease (MDRD) equation (MDRD-GFR) of less than 60 mL/min per 1.73 m2 in kidney donors. Methods: Of the 756 individuals who underwent open donor nephrectomy between 27 June 1990 and 30 April 2001, 104 had follow-up records for 50 months or more. MDRD-GFR of 60 mL/min per 1.73 m2 at final follow up divided these individuals into a normal group ( n = 78) and a CKD-GFR group ( n = 26). We compared several clinical parameters between the two groups at baseline and follow up to evaluate the risk factors for MDRD-GFR of less than 60 mL/min per 1.73 m2 in kidney donors. Results: The CKD-GFR group was significantly older than the normal group at baseline (47 ± 12 vs 41 ± 11 years old, P = 0.02). Hypertension was more prevalent in the CKD-GFR group at baseline (15% vs 2%, P = 0.005). Binary logistic regression analysis showed that age (Odds ratio (OR) 1.06, 95% confidence interval (CI) 1.01–1.10) and hypertension (OR 7.91, 95% CI 1.13–55.2) at baseline were independent risk factors for MDRD-GFR of less than 60 mL/min per 1.73 m2. At final follow up, the prevalence rates of hypertension (31% vs 8%, P = 0.006) and proteinuria (15% vs 0%, P = 0.003) were significantly higher in the CKD-GFR group. Conclusion: Older kidney donors and those with hypertension were significantly more likely to have a MDRD-GFR of less than 60 mL/min per 1.73 m2. [ABSTRACT FROM AUTHOR]

Backgrounds: Immunological staining of the transplanted kidney for C4d in peritubular capillaries (C4dPTC) has emerged as a useful method to detect antibody-mediated rejection in situ. In this retrospective study, we evaluated the prevalence of C4dPTC deposition in allograft renal biopsies diagnosed of IgA nephropathy (IgAN) and analysed its clinical significance. Method: Sixty-six biopsy specimens of post-transplant IgAN, which were obtained to evaluate azotemia and/or heavy proteinuria, were examined by immunohistochemical staining of the paraffin sections with polyclonal antibody for C4d. Results: C4d was stained positively in peritubular capillaries in 16 (24%) of the 66 cases. The C4dPTC-negative (n=50) and C4dPTC-positive groups (n=16) were not different in recipient gender, age, donor age, type of donor (living vs. cadaveric), interval from transplantation to graft biopsy (41.6± 21.8 vs. 48.3±26.1 months) and post-biopsy follow-up period (60.3±23.3 vs. 56.9±25.4 months). During the follow-up period, 12 of 50 (24%) although the incidence of graft failure was not different by the C4d deposition in peritubular capillaries, intervals from renal biopsy to graft failure tended to be shorter in C4dPTC-positive cases than C4dPTC-negative cases. In Kaplan–Meier analysis, the renal allograft function of the C4dPTC-positive group deteriorated more rapidly than that of the C4dPTC-negative group (p<0.05). Histologically, the C4dPTC-positive group had findings suggestive of acute cellular rejection more commonly than the C4dPTC-negative group (p<0.01). Conclusions: Evidence of humoral rejection, as demonstrated by C4dPTC deposition, was concurrently present in significant portions of post-transplant IgAN biopsy specimens and was associated with more rapid deterioration of renal function. These results suggest that C4dPTC positivity needs to be determined at the time of biopsy even in cases of post-transplant glomerulonephritis and immunosuppression may need to be modified accordingly. [ABSTRACT FROM AUTHOR]

Background. Glomerular endothelial cells play a role in the pathogenesis of glomerulonephritis by producing chemotactic factors. We investigated the role of NF-κB and AP-1 in tumour necrosis factor α (TNF-α) induced monocyte chemoattractant protein 1 (MCP-1) production in cultured human glomerular endothelial cells (HGEC). We also examined whether or not these processes could be modified by glucocorticoid. Methods. MCP-1 protein and mRNA levels were measured by ELISA and northern blot. NF-κB and AP-1 binding activity were assessed by electrophoretic mobility shift assay. Cytosolic IκBα and nuclear p65 protein were evaluated by western blot. For specific inhibition of NF-κB or AP-1, we used a decoy oligodeoxynucleotide. Results. TNF-α (10 ng/ml) increased MCP-1 mRNA expression in HGEC and also the release of MCP-1 protein into culture media. These effects could be partially inhibited by dexamethasone (10 nM). TNF-α induced MCP-1 production appeared to be NF-κB and AP-1 interdependent, based on the following results. (i) TNF-α increased NF-κB and AP-1 binding activity. (ii) Both NF-κB decoy oligodeoxynucleotide and AP-1 decoy oligodeoxynucleotide partially suppressed TNF-α induced MCP-1 mRNA expression. On the other hand, dexamethasone decreased TNF-α induced DNA-binding activity of AP-1 without an effect on the DNA-binding activity of NF-κB, cytosolic IκBα degradation or p65 nuclear translocation. Conclusions. These data demonstrate that while TNF-α induced MCP-1 production is mediated by the cooperative action of NF-κB and AP-1 in HGEC, dexamethasone represses TNF-α induced MCP-1 production via suppression of AP-1 binding activity. [ABSTRACT FROM AUTHOR]

Leukocyte adhesion to mesothelium is an important step during peritonitis, which is mediated by adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1). We investigated the effect of exogenous nitric oxide (NO) on VCAM-1 expression in cultured human peritoneal mesothelial cells and its signal transduction pathway. Mesothelial cells were exposed to tumor necrosis factor-α (TNF-α) in the presence or absence of NO donors, 3-morpholino-sydnonimine (SIN-1) and nitroprusside (NP). VCAM-1 mRNA and protein expression were measured by Northern blot analysis and flow cytometry. Nuclear factor-κB (NF-κB) binding activity was determined by electrophoretic mobility shift assay. Both SIN-1 and NP inhibited the TNF-α induced VCAM-1 mRNA expression in a dose dependent manner (0.25–2 mM). SIN-1 also suppressed the cell surface expression of VCAM-1 molecule. Furthermore, SIN-1 and NP inhibited the VCAM-1 mRNA expression induced by interleukin-1β or lipopolysaccharide as well. NF-κB inhibitor, PDTC dose dependently inhibited the TNF-α induced VCAM-1 mRNA expression. SIN-1 inhibited the TNF-α- induced NF-κB binding activity. Analogue of cGMP (8-bromo-cGMP) had no significant effect on TNF-α-induced VCAM-1 mRNA expression and guanylate cyclase inhibitor (ODQ) also had no significant influence on the inhibitory effect of SIN-1. These results suggest that exogenous NO inhibits VCAM-1 expression via suppression of NF-κB through a cGMP-independent pathway.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Accurate measurement of glomerular filtration rate (GFR) is critical for the management of kidney transplant recipients. Comparison of creatinine and cystatin C in renal transplant recipients gave conflicting results. We aimed to compare the performance of creatinine- and cystatin C-based equations and creatinine clearance in 102 early postoperative Korean renal transplant patients. Methods: We measured 51Cr-EDTA clearance using a 2-compartment model and considered this the reference GFR. Then, we estimated GFR using 13 creatinine- and 7 cystatin C-based equations. Serum creatinine value was calibrated to isotope-dilution mass spectrometry (IDMS). Results: The mean reference GFR was 76.77 ± 17.01 ml/min/1.73 m2. The IDMS-traceable MDRD (IDMS-MDRD) equation had the highest accuracy (94.12 within 30% of the reference; 99.02 within 50% of the reference) with a bias of 0.33 ml/min/1.73 m2 and a precision of 12.57 ml/min/1.73 m2. The Mayo Clinic equation also performed well (92.16% within 30% of the reference; 99.02% within 50% of the reference; bias: –0.19 ml/min/1.73 m2). As for cystatin C-based equations, the Filler equation had the least bias (0.03 ml/min/1.73 m2) but low accuracy (78.43% within 30% of the reference). Conclusions: We conclude that the IDMS-MDRD equation provided the best estimate of GFR in our early postoperative Korean renal transplant patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We investigated the clinical characteristics, neuroimaging findings, and final diagnosis of patients with acute isolated or prominent dysarthria who visited the emergency department (ED) between 1 January 2020 and 31 December 2021. Of 2028 patients aged ≥ 18 years with neurologic symptoms treated by a neuro-emergency expert, 75 with acute isolated or predominant dysarthria within 1 week were enrolled. Patients were categorized as having isolated dysarthria (n = 28, 37.3%) and prominent dysarthria (n = 47, 62.7%). The causes of stroke were acute ischemic stroke (AIS) (n = 37, 49.3%), transient ischemic attack (TIA) (n = 14, 18.7%), intracerebral hemorrhage (n = 1, 1.3%), and non-stroke causes (n = 23, 30.7%). The most common additional symptoms were gait disturbance or imbalance (n = 8, 15.4%) and dizziness (n = 3, 13.0%) in the stroke and non-stroke groups, respectively. The isolated dysarthria group had a higher rate of TIA (n = 7, 38.9%), single and small lesions (n = 10, 83.3%), and small-vessel occlusion in Trial of Org 101072 in acute stroke treatment (n = 8, 66.7%). Acute isolated or prominent dysarthria in the ED mostly presented as clinical symptoms of AIS, but other non-stroke and medical causes were not uncommon. In acute dysarthria with ischemic stroke, multiple territorial and small and single lesions are considered a cause.