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Background: Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown., Methods: We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR., Results: During a median follow-up duration of 65 (12-154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3-0.99 g/g (hazard ratio, 2.82; P = 0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0-2.99 g/g (P = 0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0-2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3-0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (-0.41±1.68 vs. -0.73±2.82 ml/min/1.73 m2/year, P = 0.03)., Conclusion: In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3-0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN.

Recently, there has been emerging concern that crescents, the main histologic feature of Henoch-Schönlein purpura nephritis, merely reflect active inflammation, and may not be useful in predicting long-term outcomes. We therefore conducted a single-center retrospective study to evaluate whether the new Oxford classification of immunoglobulin A nephropathy can be used to predict long-term outcome in patients with Henoch-Schönlein purpura nephritis. We included 61 biopsy-proven patients with Henoch-Schönlein purpura nephritis between January 1991 and August 2010. In addition to the International Study of Kidney Disease in Children classification, pathologic findings were also evaluated by the Oxford classification. Primary outcomes were defined as either the onset of estimated glomerular filtration rate <60 ml/min per 1.73 m(2) with ≥30% decrease in estimated glomerular filtration rate from baseline or end-stage renal disease. During a median follow-up of 49.3 months, 13 (21%) patients reached the primary end point. A Kaplan-Meier plot showed that renal event-free survival was significantly longer in patients with <50% crescents than in those with crescents in ≥50% of glomeruli (P=0.003). Among the components of the Oxford classification, patients with endocapillary hypercellularity (E1; P=0.016) and tubular atrophy/interstitial fibrosis (T1/T2; P=0.018) had lower renal survival rates than those with E0 and T0. In a multivariate Cox model adjusted for clinical and pathologic factors, E1 (hazard ratio=8.91; 95% confidence interval=1.47-53.88; P=0.017) and T1/T2 (hazard ratio=8.74; 95% confidence interval=1.40-54.38; P=0.020) were independently associated with reaching a primary outcome, whereas the extent of crescentic lesions was not. Our findings suggest that the Oxford classification can be used in predicting long-term outcomes of Henoch-Schönlein purpura nephritis.

Purpose: This study sought to evaluate the high-resolution computed tomography (HRCT) features of acute rejection and to assess the diagnostic accuracy of HRCT for acute rejection considering distribution of lesions in patients with bilateral lung transplantation (BLT)., Materials and Methods: Between March 2010 and June 2012, 48 transbronchial lung biopsies (TBLBs) and HRCT were performed simultaneously in 26 patients who underwent BLT. We evaluated the presence of ground glass opacity (GGO), consolidation, nodule, bronchial wall thickening, interlobular septal thickening, pleural effusion, atelectasis, bronchiectasis, and cardiomegaly on the HRCT images. The distribution of lesions was analyzed according to bilaterality or upper/lower predominance. Acute rejection was determined on the basis of the pathologic results of TBLB. We evaluated potential correlations of HRCT features with acute rejection, then assessed overall diagnostic accuracy of various HRCT features in combination to diagnose acute rejection in the transplanted lung., Results: Among the 48 TBLBs, 8 were diagnosed as acute rejection (A1, 4 cases; A2, 2 cases; and A3, 2 cases) pathologically. Two A1 rejections and one A2 rejection appeared normal on computed tomography images. Without considering the distribution of lesions, interlobular septal thickening was significantly associated with acute rejection (P = .010) only. Regarding the distribution of lesions on HRCT images, not only interlobular septal thickening but also GGO was significantly associated with acute rejection (P < .05). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the HRCT scan in the evaluation of acute rejection were 50%, 97.5%, 80%, 90.1%, and 89.6%, when the bilateral GGO and interlobular septal thickening with lower predominance were considered as the positive finding., Conclusions: HRCT findings considering lesion distribution could be a useful tool in diagnosing acute rejection in patients with BLT., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Many studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations., Methods: This retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR)., Results: There were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P = 0.044)., Conclusion: Similar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants.

Current medical therapies may delay chronic kidney disease progression. However, increasing experimental evidence indicates remission or even regression can be achieved. In order to study mechanisms progression vs. regression by different interventions, appropriate animal models and research design must be implemented. We review key information of selected models, including etiology, pathogenesis, procedure, time course and assessment of potential regression.

We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC) protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs) from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188), bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC) via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.

Background: To date, there has been much controversy about the role of crescentic lesion as a significant prognostic factor in immunoglobulin A nephropathy (IgAN). This study evaluated whether crescentic lesions predict adverse renal outcomes in IgAN patients., Methods: A total of 430 patients with biopsy-proven IgAN between January 2000 and December 2009 were included. Histological variables of the Oxford classification (Oxford-MEST) and the presence of crescents were assessed. The primary endpoint was a 50% decline in estimated glomerular filtration rate., Results: Of the 430 patients, 81 (18.8%) had a crescentic lesion. During a mean follow-up of 61 months, the primary outcome occurred in 19 (23.5%) patients with crescents compared with 40 (11.5%) patients without crescents (P=0.01). A Kaplan-Meier plot showed that the 10-year renal survival rate was significantly lower in patients with crescents than patients without crescents (P=0.01). However, in a multivariable Cox analysis which included clinical factors and the Oxford-MEST, crescents were not significantly associated with an increased risk of developing the primary outcome [hazard ratio: 0.71, 95% confidence interval (CI) 0.36-1.41, P=0.33]. Furthermore, adding crescents to the Oxford-MEST did not improve the discriminative ability for the prediction of renal outcomes [c-statistic: 0.86 (0.81-0.91) vs. 0.86 (0.80-0.91), P=0.21]., Conclusion: Crescentic lesion was not an independent prognostic factor, suggesting that crescents have limited value in predicting renal outcomes of IgAN.

Pathologic features can provide valuable information for determining prognosis in IgA nephropathy (IgAN). However, it is uncertain whether the Oxford classification, a new classification of IgAN, can predict renal outcome better than previous ones. We conducted a retrospective cohort study in 500 patients with biopsy-proven IgAN between January 2002 and December 2010 to compare the ability of the Haas and the Oxford classifications to predict renal outcome. Primary outcome was a doubling of the baseline serum creatinine concentration (D-SCr). During a mean follow-up of 68 months, 52 (10.4%) and 35 (7.0%) developed D-SCr and end-stage renal disease, respectively. There were graded increases in the development of D-SCr in the higher Haas classes. In addition, the primary endpoint of D-SCr occurred more in patients with the Oxford M and T lesions than those without such lesions. In multivariate Cox regression analyses, the Haas class V (HR, 12.19; P=.002) and the Oxford T1 (hazard ratio [HR], 6.68; P<.001) and T2 (HR, 12.16; P<.001) lesions were independently associated with an increased risk of reaching D-SCr. Harrell's C index of each multivariate model with the Haas and the Oxford classification was 0.867 (P=.015) and 0.881 (P=.004), respectively. This was significantly higher than that of model with clinical factors only (C=0.819). However, there was no difference in C-statistics between the 2 models with the Haas and the Oxford classifications (P=.348). This study suggests that the Haas and the Oxford classifications are comparable in predicting progression of IgAN., (© 2014.)

Background: Both palmoplantar pustulosis (PPP) and pompholyx are clinically characterized by acute eruptions of vesicles or pustules on the palms or soles., Objectives: This study aims to compare the expression of certain inflammatory mediator genes and proteins between patients with PPP and pompholyx using skin tissue samples., Methods: Skin biopsies obtained from lesional skin from patients with PPP (n = 7) and pompholyx (n = 5) were analysed by quantitative RT-PCR to measure the mRNA levels of nine genes, including IL-4, IL-8, IL-9, IL-17, IL-22, IFN-γ, CCL-20, granzyme and perforin. For immunohistochemical analysis, 34 paraffin-embedded skin specimens (PPP, n = 22; pompholyx, n = 12) were stained with anti-IL-8, IL-17A, IL-22 and granzyme B antibodies., Results: Of genes analysed, IL-8 and IL-17A mRNA expression levels were significantly higher in the PPP group than the pompholyx group (P = 0.012 in both), whereas the mRNA expression of granzyme B was significantly higher in pompholyx when compared with PPP (P = 0.004). Regarding the IL-17A immunohistochemical staining, tissue from the PPP lesions contained significantly more IL-17A(+) cells in both the epidermis and papillary dermis when compared with pompholyx (P < 0.001 and P = 0.019 respectively). Moreover, the intensity of the IL-8 immunoreactivity was also greater in the PPP skin lesions than the pompholyx tissue (P < 0.001)., Conclusions: IL-8 and IL-17A, both are increased in PPP tissue, may represent important immunologic mediators that help to differentiate this clinical entity from pompholyx. This study may provide useful clues in distinguishing PPP from pompholyx, as well as helping to understand the pathogeneses of these two diseases., (© 2013 European Academy of Dermatology and Venereology.)

Background: Pre-existing non-neoplastic renal diseases or lesions may influence patient renal function after tumor removal. However, its description is often neglected or omitted in pathologic reports. To determine the incidence and clinical significance of non-neoplastic lesions, we retrospectively examined renal tissues obtained during 85 radical nephrectomies for renal cell carcinoma., Methods: One paraffin-embedded tissue block from each case containing a sufficient amount of non-tumorous renal parenchyma was cut and processed with hematoxylin and eosin and periodic acid-Schiff methods. Non-neoplastic lesions of each histological compartment were semi-quantitatively and quantitatively evaluated., Results: Among the various histologic lesions found, tubular atrophy, arterial intimal thickening, and glomerulosclerosis were the most common (94.1%, 91.8%, and 88.2%, respectively). Glomerulosclerosis correlated with estimated glomerular filtration rate at the time of surgery, as well as at 1- and 5-years post-surgery (p=.0071), but tubulointerstitial fibrosis or arterial fibrous intimal thickening did not. Post-hoc analysis revealed that glomerulosclerosis of more than 20% predicted post-operative renal function. However, its significance disappeared when gender and age were considered., Conclusions: In conclusion, non-neoplastic lesions, especially with regard to glomerulosclerosis percentage, should be described in pathology reports to provide additional information on renal function decline.

Background: In contrast with deceased donor transplantation, the clinical significance of pathologic findings in time-zero biopsies after living donor kidney transplantation are rarely reported, due to the expectation that histologic findings and renal function are normal. The aim of this study was to identify subclinical pathologic findings in living donors and examine the effect on early graft renal function., Methods: Between December 2006 and July 2011, 146 living-donor kidney transplant recipients were enrolled in this study. We retrospectively analyzed donor and recipient-related clinical parameters, and post-transplant 6 months and 1 year estimated glomerular filtration rate (eGFR) as early graft renal function. Time-zero biopsies were evaluated using the 2007 Banff criteria., Results: Most abnormal histologic findings were of mild degree as determined by Banff scores. Global glomerulosclerosis (GS, 35.6%), tubular atrophy (CT, 36.3%), interstitial fibrosis (CI, 20.5%), vascular fibrous intimal thickening (CV, 4.1%), arteriolar hyaline thickening (AH, 14.4%), interstitial inflammation (I, 3.4%) were pathologic findings in time-zero biopsies. The univariate analysis revealed that donor age and gender were significantly associated with eGFR at post-transplant 6 months and at 1 year (P < .05). Furthermore, GS and CT were significantly associated with early graft renal function (P < .05). However, multivariate linear regression analysis showed only donor age was significantly associated with early graft renal function (P = .001)., Conclusion: A mild degree of subclinical, pathologic findings on time-zero biopsy did not affect early graft renal function in living-donor kidney transplantation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Hyperglycemia exacerbates renal ischemia-reperfusion (IR) injury via aggravated inflammatory response and excessive production of reactive oxygen species. This study aimed to investigate the ability of propofol, a known antioxidant, to protect kidneys against IR injury in hyperglycemic rats in comparison with normoglycemic rats., Methods: Sixty rats were randomly assigned to four groups: normoglycemia-etomidate, normoglycemia-propofol, hyperglycemia-etomidate, and hyperglycemia-propofol. Anesthesia was provided with propofol or etomidate depending on the group. Also, the rats received 1.2 g/kg dextrose or the same volume of normal saline depending on the group. Renal ischemia was induced for 25 min. The rats were killed, and samples were collected 65 min after starting intravenous anesthetics (sham) and 15 min and 24 h after reperfusion injury to compare the histologic degree of renal tubular damage and levels of inflammatory markers and enzymes related to reactive oxygen species., Results: Compared with etomidate, propofol significantly attenuated tubular damage after reperfusion in hyperglycemic rats. Also, tubular damage was greater under hyperglycemia compared with normoglycemia in the etomidate group, whereas it was similar in the propofol group. Propofol preserved superoxide dismutase level and attenuated the increase in levels of myeloperoxidase, interlukin-1β, and tumor necrosis factor-α after reperfusion compared with etomidate especially in hyperglycemic rats. Propofol also attenuated the production of inducible nitric oxide synthase and phosphorylation of inhibitor of κB and nuclear factor-κB after reperfusion, which were more prominent under hyperglycemia., Conclusions: Propofol conveyed renoprotection against IR injury by preserved antioxidation ability and attenuated inflammatory response, which were more prominent under hyperglycemia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: This study was designed to evaluate the efficacy of a fat clearing technique for accurate nodal staging of rectal cancer patients after preoperative chemoradiotherapy (CRT)., Methods: A total of 19 patients with rectal cancer within 10 cm from anal verge were divided into two groups: non-CRT group (n = 10) and CRT group (n = 9). For pathologic assessment, lymph node (LN) harvest was performed using conventional manual dissection followed by a fat clearing technique., Results: A median of 3.0 additional LNs in non-CRT group and 3.8 LNs in CRT group were identified by the fat clearing technique. When subanalysis was performed in patients with fewer than 12 retrieved LNs, a median of 4.0 extra LNs in non-CRT group and 3.5 extra LNs in CRT group were identified after the fat clearing technique. None of additionally identified nodes were metastatic. In both groups, the median size of retrieved LNs following the fat clearing technique was smaller than that obtained by manual dissection (2.0 mm vs. 3.0 mm, P < 0.001)., Conclusion: The fat clearing technique allowed detection of additional LNs that were missed by the manual method, but these detected LNs were not proven to be metastatic.

The pathogenic role of T cells in hypertension has been documented well in recent animal studies. However, the existence of T-cell-driven inflammation in human hypertension has not been confirmed. Therefore, we undertook immunologic characterization of T cells from patients with hypertension and measured circulating levels of C-X-C chemokine receptor type 3 chemokines, which are well-known tissue-homing chemokines for T cells. We analyzed immunologic markers on T cells from patients with hypertension by multicolor flow cytometry. We then measured circulating levels of the C-X-C chemokine receptor type 3 chemokines, monokine induced by γ interferon (IFN), IFN γ-induced protein 10, and IFN-inducible T-cell α chemoattractant, in patients with hypertension and in age- and sex-matched control subjects by the cytometric bead array method. In addition, we examined histological features of IFN-inducible T-cell α chemoattractant expression from renal biopsy specimens of patients with hypertensive nephrosclerosis and control subjects. The total T-cell population from patients with hypertension showed an increased fraction of immunosenescent, proinflammatory, cytotoxic CD8(+) T cells. Circulating levels of C-X-C chemokine receptor type 3 chemokines were significantly higher in patients with hypertension than in control subjects. Furthermore, immunohistochemical staining revealed increased expression of the T-cell chemokine, IFN-inducible T-cell α chemoattractant, in the proximal and distal tubules of patients with hypertensive nephrosclerosis. Immunosenescent CD8(+) T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension, suggesting a role for T-cell-driven inflammation in hypertension. A more detailed characterization of CD8(+) T cells may offer new opportunities for the prevention and treatment of human hypertension.

The aberrant expressions of casein kinase 2 (CK2) was found in prostate cancer patient and cell lines, but little is known of the detailed mechanisms implicated in prostate tumorigenesis. In this study, we report that both CK2 activity and CK2-mediated NCoR phosphorylation are significantly elevated in the androgen-independent prostate cancer cell line DU145 and PC-3 compared with RWPE1 and LNCaP cells. Increased phosphorylation inversely correlates with the mRNA level of the NCoR-regulated gene, interferon-γ-inducible protein 10 (IP-10). CK2 inhibition abrogated NCoR phosphorylation, IP-10 transcriptional repression, and the invasion activity of PC-3 cells. Inhibition of the CK2-NCoR network significantly reduced in vivo PC-3 cell tumorigenicity, likely due to transcriptional derepression of IP-10. Clinicopathological analyses revealed that increased CK2-mediated NCoR phosphorylation significantly correlates with poor survival among prostate cancer patients. These findings elucidate a CK2-modulated oncogenic cascade in prostate tumorigenesis.

Background: We explored the efficacy of the Oxford classification for assessing native immunoglobulin A nephropathy (IgAN) in posttransplantation patients compared with the glomerular injury score and Haas classification., Methods: A total of 125 renal allograft biopsies obtained from 114 patients diagnosed with IgAN regardless of original disease were assessed., Results: The average time to biopsy was 70.5±45.3 months after transplantation. Glomeruli showed normal histology in 18.4%. Mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), and tubulointerstitial fibrosis (T1-2) were present in 12.8%, 6.4%, 45.6%, and 20.8% of the samples, respectively. There was a significant correlation between Oxford-MEST scores and glomerular injury score or Haas subclass. S1 and T1-2 were correlated with elevated serum creatinine level, proteinuria, and decreased estimated glomerular filtration rate, and E1 was correlated with decreased estimated glomerular filtration rate at the time of biopsy. The 10- and 15-year graft survival rates were 62.9% and 34.3%, respectively. The graft survival rate was significantly lower in the presence of S1 and T1-2. Endocapillary hypercellularity, segmental sclerosis, and tubulointerstitial fibrosis predicted graft survival and endocapillary hypercellularity and tubulointerstitial fibrosis also predicted serum creatinine doubling., Conclusions: The Oxford classification scheme is useful for evaluating chronic graft dysfunction in patients with posttransplantation IgAN. In addition to tubulointerstitial fibrosis, the presence of endocapillary hypercellularity and segmental sclerosis should be included in the pathology report.

The final destination point of nanoparticles is the environment, where they remain a long period; therefore, a deep understanding of the relationship between nanoparticles and the environmental factors is required. Japanese medaka embryos were exposed to two differently prepared AgNPs: freshly prepared AgNPs and aged AgNPs. With these two AgNP preparations, we studied the impacts of humic acid in terms of embryonic toxicity, as well as the behavior of AgNPs. Aged AgNPs exhibited a lower lethal concentration (LC50) value (1.44mg/L) compared to fresh AgNPs (3.53mg/L) through 96h acute toxicity tests, due to the release of silver ions, as confirmed by kinetic analysis. The presence of humic acids considerably reduced the toxicity of aged AgNPs due to complexation with silver ions. Agglomeration, induced by interactions with humic acid, might reduce the bioavailability of AgNPs to Japanese medaka embryos. This study demonstrates that aged AgNPs releasing more silver ions are more toxic than fresh AgNPs, and humic acids play a role in reducing the toxicity of aged AgNPs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Copepoda is the most diverse and abundant group of crustaceans, but its phylogenetic relationships are ambiguous. Mitochondrial (mt) genomes are useful for studying evolutionary history, but only six complete Copepoda mt genomes have been made available and these have extremely rearranged genome structures. This study determined the mt genome of Calanus hyperboreus, making it the first reported Arctic copepod mt genome and the first complete mt genome of a calanoid copepod. The mt genome of C. hyperboreus is 17,910 bp in length and it contains the entire set of 37 mt genes, including 13 protein-coding genes, 2 rRNAs, and 22 tRNAs. It has a very unusual gene structure, including the longest control region reported for a crustacean, a large tRNA gene cluster, and reversed GC skews in 11 out of 13 protein-coding genes (84.6%). Despite the unusual features, comparing this genome to published copepod genomes revealed retained pan-crustacean features, as well as a conserved calanoid-specific pattern. Our data provide a foundation for exploring the calanoid pattern and the mechanisms of mt gene rearrangement in the evolutionary history of the copepod mt genome., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Fetal adenocarcinoma is a rare adenocarcinoma subtype of pulmonary blastoma. A 48-year-old male patient is being referred to our hospital due to progressive dyspnea. A chest X-ray showed a lung mass of unknown origin that was obstructing the right main bronchus. After relieving the airway obstruction with stent insertion via bronchoscopy, a diagnosis of fetal adenocarcinoma is being confirmed through thoracoscopic biopsy. Due to the locally advanced state of the lung cancer, it seemed to be inoperable, and concurrent chemo-radiation therapy was being administered with docetaxel. The stent was removed after improvements in the airway obstruction followed by a lung mass shrinkage. Comparing to other contexts which describe fetal adenocarcinoma as lower grade malignancy with low-associated mortality, herein, we describe a case of locally-advanced fetal adenocarcinoma (T4N3M0). This is the first documented case being treated with concurrent chemoradiation therapy. The followed-up image studies represent a partial response and the patient is currently under further observations.

Nephrotic syndrome (NS) rarely occurs after hematopoietic stem cell transplantation (HSCT) as a late manifestation of graft-versus-host disease (GVHD). Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD.

Background: To define the exact boundary of the intrathyroid and extrathyroid aspects of a gland when determining the extent of cancer invasion, we plan to clarify the definition of sizable vascular structures, which is one of the helpful histologic clues in determining a minimal extrathyroid extension. We hypothesized that arterial wall thicknesses in extrathyroid soft tissue would be significantly different from the arteries in the thyroid parenchyma., Methods: Twenty cases of papillary carcinoma were selected. The numbers and wall thicknesses of the arteries and arterioles in intrathyroid and extrathyroid tissue were evaluated. The absence of nerve tissue in the thyroid gland was confirmed using the S-100 protein immunohistochemical stain., Results: The comparison of the mean thicknesses of the total arteries between the extrathyroid and intrathyroid tissues in the retrospective study (26.88 µm vs. 15.07 µm, respectively) and the prospective study (35.24 µm vs. 16.52 µm, respectively) revealed significant differences (p=0.000). The greatest thickness of the intrathyroid arteries was 67.93 µm., Conclusions: According to our results, the study showed that the extrathyroidal arteries were significantly thicker than the intrathyroidal arteries. We suggest that the sizable blood vessels of extrathyroidal arteries should be greater than 67.93 µm in thickness.

In Korea, more than 80% of municipal wastewater treatment plants (WWTPs) with capacities of 500 m3·d-1 or more are capable of removing nitrogen from wastewater through biological nitrification and denitrification processes. Normally, these biological processes show excellent performance, but if a toxic chemical is present in the influent to a WWTP, the biological processes (especially, the nitrification process) may be affected and fail to function normally; nitrifying bacteria are known very vulnerable to toxic substances. Then, the toxic compound as well as the nitrogen in wastewater may be discharged into a receiving water body without any proper treatment. Moreover, it may take significant time for the process to return back its normal state. In this study, a DO- and pH-based strategy to identify potential nitrification inhibition was developed to detect early the inflow of toxic compounds to a biological nitrogen removal process. This strategy utilizes significant changes observed in the oxygen uptake rate and the pH profiles of the mixed liquor when the activity of nitrifying bacteria is inhibited. Using the strategy, the toxicity from test wastewater with 2.5 mg·L-1 Hg2+, 0.5 mg·L-1 allythiourea, or 0.25 mg·L-1 chloroform could be successfully detected.

Objective: Inhibition of the receptor for advanced glycation end products (RAGE) may attenuate the systemic inflammatory response and ensuing severe sepsis. We report an investigation into the effect of soluble RAGE (sRAGE)-Fc fusion protein in severe sepsis induced by a cecal ligation and puncture (CLP) procedure., Materials and Methods: The experiment was performed using CLP control mice, mice treated with 0.5 or 1.0 μg sRAGE-Fc fusion protein, and sham surgery mice., Results: Survival benefits over the CLP control group were evident (P = 0.036) in mice given 1.0 μg sRAGE-Fc fusion protein. In addition, the pulmonary inflammation score in the sRAGE-Fc fusion protein-treated group was significantly lower than that in the CLP control group (P < 0.05). Lung tissue in the sRAGE-Fc fusion protein-treated group revealed a significant decrease in the expression of inflammatory cytokines. Furthermore, levels of interleukin (IL)-1β and tumor necrosis factor-α were significantly lower in sRAGE-Fc fusion protein treated groups (P < 0.001). Moreover, IL-6 levels showed a significant difference between CLP control and sRAGE-Fc fusion protein treated groups (P < 0.01)., Conclusions: sRAGE-Fc fusion protein has beneficial effects in a standard murine model of polymicrobial, intra-abdominal severe sepsis.

The purpose of this study was to investigate the clinical, laboratory, and pathologic characteristics of dense deposit disease (DDD) in Korean children and to determine whether these characteristics differ between Korean and American children with DDD. In 2010, we sent a structured protocol about DDD to pediatric nephrologists throughout Korea. The data collected were compared with previously published data on 14 American children with DDD. Korean children had lower 24-hr urine protein excretion and higher serum albumin levels than American children. The light microscopic findings revealed that a higher percentage of Korean children had membranoproliferative glomerulonephritis patterns (Korean, 77.8%; American, 28.6%, P = 0.036), whereas a higher percentage of American children had crescents (Korean, 0%; American, 78.6%, P < 0.001). The findings from the electron microscopy revealed that Korean children were more likely to have segmental electron dense deposits in the lamina densa of the glomerular basement membrane (Korean, 100%; American, 28.6%, P = 0.002); mesangial deposit was more frequent in American children (Korean, 66.7%; American, 100%, P = 0.047). The histological findings revealed that Korean children with DDD were more likely to show membranoproliferative glomerulonephritis patterns than American children. The degree of proteinuria and hypoalbuminemia was milder in Korean children than American children.

Bronchiolitis obliterans (BO) is a late onset complication of allogeneic hematopoietic stem cell transplantation (HSCT), and treatment outcome is dismal if it does not respond to immunosuppressive therapy. A 21-year-old male diagnosed with acute myeloid leukemia received an allogeneic HSCT from human leukocyte antigen- identical sibling donor. Twenty one months after transplantation, he developed progressive dyspnea and was diagnosed BO. Despite standard immunosuppressive therapy, the patient rapidly progressed to respiratory failure and Novalung® interventional lung-assist membrane ventilator was applied in the intensive care unit. Three months after the diagnosis of BO, the patient underwent bilateral lung transplantation (LT) and was eventually able to wean from the ventilator and the Novalung®. Since the LT, the patient has been under a strict rehabilitation program in order to overcome a severe lower extremity weakness and muscle atrophy. Histologic findings of the explanted lungs confirmed the diagnosis of BO. Nine months after the LT, the patient showed no signs of rejection or infectious complications, but still required rehabilitation treatment. This is the first LT performed in a patient with BO after allogeneic HSCT in Korea. LT can be an effective therapy in terms of survival for patients with respiratory failure secondary to development of BO following HSCT.

Background: Examination of urine for decoy cells (DCs) is a useful screening test for polyomavirus (PV) activation. We explored the significance of the amount of DCs in persistent shedding, PV nephropathy and acute rejection., Methods: A case-controlled study was performed in 88 renal allograft patients who had DCs detected at least once in four or more urine samples., Results: Fifty one patients were classified into the high-grade shedding group (HG) and 37 patients into the low-grade shedding group (LG) according to DC shedding (≥10 or <10 DCs/10 high power field [HPF]). DC shedding of more than three consecutive months was significantly more prevalent in the HG as compared with their LG counterparts (p<0.0001). Urinary DCs were present for more than one year in 29.4% of the HG and 8.1% of the LG. Real-time polymerase chain reaction for PV was higher in both urine (51.4% vs. 11.1%) and plasma (9.1% vs. 0%) of the HG than the LG. The prevalence of PV nephropathy was higher in the HG than the LG (p=0.019). However, there was no significant difference in the prevalence of acute rejection., Conclusions: Shedding of ≥10 DCs/10 HPF is associated with sustained shedding, polymerase chain reaction positivity and PV nephropathy, but not a predictor of acute rejection.

Transplant glomerulopathy (TG) a morphological feature of chronic active antibody-mediated rejection, is associated with donor-specific antibody, peritubular capillary deposition of C4d, and multilayering of peritubular capillary basement membranes. To evaluate the significance of accompanying nonimmunologic injuries in TG, we retrospectively reviewed 2839 renal allograft cases at our institute among which TG was diagnosed in 81 patients (2.9%). Among TG cases, 48 samples showed accompanying diseases such as chronic calcineurin inhibitor toxicity, hepatitis viral infection, posttransplant diabetes, and glomerulonephritis. Comparing the pure form of TG with TG-mixed diseases, there was no difference in patient demography, serum creatinine values, and proteinuria. Among histological parameters, severe hyalinosis was more frequently observed among the TG plus other diseases group. The two groups did not show significant difference in graft survival (P = .216)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Membranous nephropathy (MN) may develop as recurrence or de novo after transplantation. Recently, autoimmune or alloimmune responses to unspecified glomerular antigens have been considered as a pathogenetic mechanism. To explore the relationship between antibody-mediated injury and posttransplantation MN, we tested C4d positivity using polyclonal antibody in renal allograft biopsy samples diagnosed as posttransplantation MN. A total of 19 cases (16 males and 3 females), including 2 recurrent and 7 de novo forms, were the subject of the study. On light microscopy, stage II was the most common (n = 9). In addition to glomerular capillary immunoglobulin (Ig)G deposits, all but 2 cases having only sclerotic glomeruli were C4d-positive in glomerular capillary walls. Twelve cases were also positive in cortical peritubular capillaries (PTCs): diffuse in 8 cases and focal in 4 cases. Two of 3 cases associated with acute rejection and 3 of 4 cases associated with chronic rejection were PTC C4d-positive. The frequency of C4d positivity in PTCs was significantly higher than that of posttransplantation IgA nephropathy (P = .028). In conclusion, a higher frequency of PTC C4d positivity suggests an involvement of chronic antibody-mediated injury in the evolution of posttransplantation MN., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background and Objectives: Nephrotic syndrome (NS) is a rare manifestation of IgA nephropathy (IgAN). Clinical characteristics and long-term outcomes of this condition have not yet been explored., Design, Setting, Participants, & Measurements: A multicenter observational study was conducted between January 2000 and September 2010 in 1076 patients with biopsy-proven IgAN from four medical centers in Korea. The primary outcome was a doubling of the baseline serum creatinine concentration., Results: Of the 1076 patients, 100 (10.2%) presented with NS; complete remission (CR), partial remission (PR), and no response (NR) occurred in 48 (48%), 32 (32%), and 20 (20%) patients, respectively. During the median follow-up of 45.2 months, 24 patients (24%) in the NS group reached the primary endpoint compared with 63 (7.1%) in the non-NS group (P<0.001). The risk of reaching the primary endpoint was significantly higher in the PR (P=0.04) and NR groups (P<0.001) than in the CR group. Among patients with NS, 24 (24%) underwent spontaneous remission (SR). SR occurred more frequently in female patients and in patients with serum creatinine levels ≤1.2 mg/dl and a >50% decrease in proteinuria within 3 months after NS onset. None of the patients with SR reached the primary endpoint and they had fewer relapses during follow-up., Conclusions: This study demonstrated that the prognosis of NS in IgAN was not favorable unless PR or CR was achieved. In addition, SR was more common than expected, particularly in patients with preserved kidney function and spontaneous decrease in proteinuria shortly after NS onset.

Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by periodic episodes of fever and recurrent polyserositis. It is caused by a dysfunction of pyrin (or marenostrin) as a result of a mutation within the MEFV gene. It occurs mostly in individuals of Mediterranean origin; however, it has also been reported in non-Mediterranean populations. In this report, we describe the first case of FMF in a Korean child. As eight-year-old boy presented recurrent febrile attacks from an unknown cause, an acute scrotum and renal amyloidosis. He also showed splenomegaly, lymphadenopathy, pleural effusion, ascites and elevated acute phase reactants. After MEFV gene analysis, he was diagnosed as FMF combined with amyloidosis.

As a continuation of our previous report (J. Comb. Chem.2010, 12, 548-558), we accomplished the diversity-oriented synthesis of polyheterocyclic small-molecule library with privileged benzopyran substructure. To ensure the synthetic efficiency, we utilized the solid-phase parallel platform and the fluorous-tag-based solution-phase parallel platform to construct a 284-member polyheterocyclic library with six distinct core skeletons with an average purity of 87% on a scale of 5-10 mg. This library was designed to maximize the skeletal diversity with discrete core skeletons in three-dimensional space and the combinatorial diversity with four different benzopyranyl starting materials and various building blocks. Together with our reported benzopyranyl library, we completed the construction of polyheterocyclic benzopyran library with 11 unique scaffolds and their molecular diversity was visualized in chemical space using principle component analysis (PCA).

Although cisplatin is a highly effective antineoplastic agent, nephrotoxicity is its major clinical problem. Recently, it was reported that Spirulina, a blue-green algae, has potent antioxidant properties. The aim of this study was to establish the possible protective role of C-phycocyanin (PC), one of the active ingredients of Spirulina, against cisplatin-induced nephrotoxicity. This study was carried out using human kidney-2 (HK-2) cells and male C57BL6 mice. Cells and mice were divided into four groups; untreated control group, PC-treated control group, cisplatin-treated group, and PC plus cisplatin-treated group. The molecular, functional, and structural parameters were measured. PC significantly attenuated blood urea nitrogen, serum creatinine, renal histological damages, and apoptotic cell death in cisplatin-treated mice. The cisplatin-induced cell death was significantly attenuated in cells pretreated with PC. PC also significantly attenuated the elevation of p-ERK, p-JNK, and p-p38 induced by cisplatin treatment. The expression of Bax, caspase-9, and caspase-3 in cisplatin-treated cells were also decreased by PC treatment. In conclusion, PC ameliorates cisplatin-induced nephrotoxicity and, at least in part, suppression of p-ERK, p-JNK, p-p38, Bax, caspase-9, and caspase-3 may be involved in this mechanism.

Background and Aims: Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN., Methods: A total of 343 patients with biopsy-proven IgAN were enrolled between January 2000 and December 2008. Decreased serum C3 level (hypoC3) was defined as C3 <90 mg/dl. The study endpoint was end-stage renal disease (ESRD) and a doubling of the baseline serum creatinine (D-SCr)., Results: Of the patients, there were 66 patients (19.2%) with hypoC3. During a mean follow-up of 53.7 months, ESRD occurred in 5 patients (7.6%) with hypoC3 compared with 9 patients (3.2%) with normal C3 levels (P = 0.11). However, 12 patients (18.2%) with hypoC3 reached D-SCr compared with 17 patients (6.1%) with normal C3 levels [Hazard ratio (HR), 3.59; 95% confidence interval (CI), 1.33-10.36; P = 0.018]. In a multivariable model in which serum C3 levels were treated as a continuous variable, hypoC3 significantly predicted renal outcome of D-SCr (per 1 mg/dl increase of C3; HR, 0.95; 95% CI, 0.92-0.99; P = 0.011). The risk of reaching renal outcome was significantly higher in patients with mesangial C3 deposition 2+ to 3+ than in patients without deposition (HR 9.37; 95% CI, 1.10-80.26; P = 0.04)., Conclusions: This study showed that hypoC3 and mesangial C3 deposition were independent risk factors for progression, suggesting that complement activation may play a pathogenic role in patients with IgAN.

Background: Corticotropin-releasing hormone (CRH) is the central regulating hormone of the hypothalamic-pituitary-adrenal axis. CRH also has diverse functional effects in the periphery and is related to the aggravation of several cutaneous diseases; however, the effect of CRH on T cells in patients with atopic dermatitis (AD) has not been well evaluated., Objective: We investigated whether CRH directly affects peripheral T(H)1, T(H)2, and regulatory T (Treg) cells in patients with AD., Methods: We assessed whether T cells express the CRH receptor protein and mRNA by using flow cytometry, Western blotting, immunofluorescence, immunohistochemistry, and RT-PCR. We evaluated cytokine expression using ELISA after treating the T cells extracted from patients with AD and healthy control subjects (HCs) with CRH. Flow cytometry was then used to evaluate any direct effects of CRH on T(H)1, T(H)2, and Treg cells from patients with AD and HCs., Results: T cells from patients with AD expressed significantly lower CRH receptor 1/2 mRNA levels than T cells from HCs. T cells from HCs reacted with different IL-4 and IFN-γ secretions to CRH treatment, whereas T cells from patients with AD did not. IL-10 production was significantly decreased in the supernatants from both the HCs and patients with AD after CRH treatment. CRH upregulated IL-4 production by T(H)2 cells and downregulated IFN-γ production by T(H)1 cells in HCs. CRH also suppressed the production of IL-10 by forkhead box protein 3-negative Treg cells in both groups, but the difference was only significant in patients with AD., Conclusions: CRH-mediated suppression of IL-10 secretion from Treg cells might explain stress-related exacerbations in patients with AD., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

There is no scientific evidence to support the idea that serial sectioning along the short axis of the lymph node is superior to a single bisection along the long axis. We mathematically evaluated methods of lymph node dissection and applied the result to six lymph nodes that had produced false negative results at the time of frozen examination. We simplified the geometry of a lymph node to that of a three-dimensional ellipse and compared two different cutting methods. Let A be the cross-sectional area obtained through a single bisection along the long axis, and let B be the sum of the cross-sectional areas of n fragments obtained via serial cutting along the short axis. The smallest n (n*) that makes a B larger than A can be calculated. n* = [3L + √9L² + 16S²)/4S]. ([α], the smallest integer greater than or equal to α; L, long axis; S, short axis). The probabilities of tumor detection when the node is bisected along the long axis (P(D(A)|E)) and when serially cut along the short axis (P(D(B)|E)) are as follows. P(D(A)|E = {(3/2)S² - 3ST + T²}T/(S - T)³. and P(D(B)|E) = (n - 1){(1 + 1/n)L² - 3LT + T²}T/(L - T)³. (T, size of the tumor cell cluster). According to these formulas, three out of six lymph nodes were not examined in the most appropriate manner., (© 2011 The Authors. APMIS © 2011 APMIS.)

Background: AEB071 (sotrastaurin) is a specific inhibitor of protein kinase C that prevents T-cell activation. Our previous study demonstrated that AEB071 monotherapy could prevent acute cardiac allograft rejection in rats. Herein, we investigated the effects of AEB071 combined with various doses of tacrolimus (Tac) on the allograft rejection and survival in a rat heart transplantation model., Materials and Methods: Heterotopic cardiac transplantation from Brown-Norway to Lewis rats was performed. Cardiac allograft survival was assessed by monitoring heartbeats in six recipients of each experimental group. Another four recipient rats were selectively sacrificed in each group at d 7 post-transplantation for histologic examination. Serum transaminases, blood urea nitrogen, and creatinine concentrations were measured., Results: AEB071 monotherapy prolonged allograft mean survival time (MST) compared with the untreated control group. Also a combination of AEB071 and Tac prolonged MST compared with monotherapy groups with higher dose of Tac. In the cardiac graft histology, AEB071 combined with Tac 0.6 mg/kg/d significantly decreased the rejection grade as indicative of decreased inflammatory cell infiltration into the graft. No experimental group was found with any abnormal histologic or serologic evidence of liver and kidney toxicity., Conclusion: AEB071 combined with a smaller dosage of Tac may be clinically possible to establish calcineurin inhibitor (CNI) minimization protocol in solid organ transplantation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Renin-angiotensin system activation is involved in inflammation and fibrosis in the kidney. Aliskiren, a direct renin inhibitor, decreases renin-angiotensin system activation, including plasma renin activity and angiotensin II, but increases the prorenin level, which may promote inflammation and fibrosis in renal tissue. Thus, we evaluated whether inhibiting the renin-angiotensin system by aliskiren would decrease renal inflammation and fibrosis in a mouse model of unilateral ureteral obstruction., Materials and Methods: Ten-week-old male C57BL/6 mice (Samtako, Kyoung Gi-Do, Korea) weighing 30 to 33 gm were divided into 4 groups, including vehicle or aliskiren treated sham operated and vehicle or aliskiren treated unilateral ureteral obstruction groups. We evaluated plasma renin activity, and plasma renin and renal mRNA expression levels of renin and (pro)renin receptor. To evaluate inflammation and fibrosis renal mRNA expression of monocyte chemotactic protein-1, osteopontin and transforming growth factor-β was measured. Hematoxylin and eosin, Masson's trichrome staining, and immunohistochemical staining for CD68, transforming growth factor-β and α-smooth muscle actin were performed., Results: Plasma renin activity was significantly lower in the aliskiren treated obstruction group than in the vehicle treated obstruction group. Aliskiren treatment increased renal mRNA expression of renin. The number of CD68 positive cells, and renal monocyte chemotactic protein-1 and osteopontin mRNA levels were significantly higher in mice with unilateral ureteral obstruction than in sham operated mice. Aliskiren decreased the increased levels of these inflammation markers. Aliskiren also decreased renal transforming growth factor-β mRNA expression, transforming growth factor-β and α-smooth muscle actin immunostaining, and Masson's trichrome stained areas of unilateral ureteral obstruction kidneys., Conclusions: Aliskiren has anti-inflammatory and antifibrotic effects in an experimental unilateral ureteral obstruction mouse model., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Deposition of polymeric IgA1 in the kidney mesangium is the hallmark of IgA nephropathy, but the molecular mechanisms of IgA-mediated mesangial responses and inflammatory injuries remain poorly understood. We hypothesize that Toll-like receptor 4 (TLR4) is involved in IgA-induced mesangial cell activation., Materials and Methods: Mouse mesangial cells were stimulated with lipopolysaccharide (LPS) (1 μg/mL), IgA (20 μg/mL), or both, and TLR4 expression was measured by real time RT-PCR and Western blot. Intracellular responses to LPS or IgA were assessed by Western blot for ERK1/2, JNK, p38 MAP kinases (MAPKs), Iκ-Bα degradation and fibronectin secretion. MCP-1 secretion was assessed by ELISA. Small interfering RNA (siRNA) of TLR4 was used to confirm that the effects were caused by TLR4 activity., Results: LPS- or IgA-treatment upregulated the levels of TLR4 mRNA and protein in cultured MMC at 24 h. LPS and IgA induced rapid phosphorylation of MAPKs, but degradation of Iκ-Bα was observed only in LPS-treated MMC. LPS, but not IgA, induced increased secretion of MCP-1 and fibronectin at 24 h or 48 h. Combined LPS and IgA treatment did not cause additional increases in TLR4 mRNA and protein levels or Iκ-Bα degradation, and MCP-1 and fibronectin secretions were less than with LPS alone. LPS- or IgA-induced TLR4 protein levels and MAPK activation were inhibited by transfection with TLR4 siRNA., Conclusion: These results indicate that the activation of MAPKs and MCP-1 secretion are mediated by TLR4, at least in part, in IgA-treated mesangial cells. TLR4 is involved in mesangial cell injury by induction of pro-inflammatory cytokines in IgA nephropathy.

Background: Type I interferon (IFN) has been reported to have an important role in the development of cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). A new subset of CD4+ T cells, T helper (Th)17 cells, also plays a role in the development of autoimmunity., Aim: To investigate expression of interleukin (IL)-17 and IFN-α in different CLE subsets, and their associations with the pathogenesis of LE., Methods: Skin tissue samples from 33 cases, including chronic discoid LE (n = 24), acute (A)CLE (n = 4), subacute CLE (n = 1) and lupus panniculitis (n = 4) were collected for immunohistochemistry. Expression of IL-6, IL-17A, IFN-α, IFN-γ, myxovirus protein (Mx)A and transforming growth factor (TGF)-β was assessed in these samples., Results: All LE specimens had staining for IL-6 and TGF-β in the infiltrated inflammatory cells. IL-17A staining was seen in 84.8% of specimens, and IFN-α or MxA was seen in 93.9%. TGF-β expression in ACLE was significantly greater than that in both chronic cutaneous (CC)LE and in lupus panniculitis (P = 0.02 for both). Expression of IL-17A was positively associated with expression of IFN-α and MxA (Spearman's ρ = 0.56 and 0.39, respectively). In addition, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) correlated positively with expression of IFN-α and MxA (ρ = 0.40 for both), whereas there was no correlation with IL-17A expression., Conclusions: Two major cytokines, IL-17A and IFN-α, may play roles in the pathogenesis of CLE. Their patterns of expression positively correlated with each other., (© The Author(s). CED © 2011 British Association of Dermatologists.)

The influence of salinity and organic matter on the distribution coefficient (K(d)) for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in a brackish water-clay system was studied. The distribution coefficients (K(d)) for PFAs onto inorganic clay surfaces increased with salinity, providing evidence for electrostatic interaction for the sorption of PFAs, whereas the relationship between K(d) and organic carbon content (f(oc)) suggested that hydrophobic interaction is the primary driving force for the sorption of PFAs onto organic matter. The organic carbon normalized adsorption coefficient (K(oc)) of PFAs can be slightly overestimated due to the electrostatic interaction within uncoated inorganic surfaces. In addition, the dissolved organic matter released from coated clay particles seemed to solvate PFA molecules in solution, which contributed to a decrease in K(d). A positive relationship between K(d) and salinity was apparent, but an empirical relationship for the 'salting-out' effect was not evident. The K(d) values of PFAs are relatively small compared with those reported for persistent organic pollutants. Thus, sorption may not be a significant route of mass transfer of PFAs from water columns in estuarine environments. However, enhancement of sorption of PFAs to particulate matter at high salinity values could evoke potential risks to benthic organisms in estuarine areas.

Aims: To identify the predictive factors for ciclosporin A (CyA)-associated nephrotoxicity (CAN) in children with minimal change nephrotic syndrome (MCNS)., Methods: The clinical and laboratory findings of 58 children (median age 3.2 years, range 1.1-13.1 years, male:female 48:10) with MCNS who were treated with CyA from 1992 to 2002 were analysed retrospectively. Forty-eight (83%) of them were steroid dependent and 10 (17%) were steroid resistant. The starting dose of CyA was 5mg/kg per day, and the desired drug level was kept at 100-200 ng/ml. Serial renal biopsies were performed before and after CyA therapy., Results: Twenty-two patients (38%) had CAN (group I) and 36 (62%) did not (group II). There were no differences in the age at onset, sex, initial response to steroids, duration of CyA therapy and relapse rates. However, the median CyA trough levels were significantly higher in group I than in group II (218.0±15.2 vs 171.8±6.7 ng/ml, p=0.01). Changes in creatinine clearance were more decreased in group I than in group II (-39.4±8.2 vs 2.7±4.3 ml/min per 1.73m(2), p<0.0001). Multiple logistic regression analysis also revealed the median CyA trough level was an independent risk factor for the development of CAN (OR 1.025, 95% CI 1.007 to 1.044, p=0.007)., Conclusions: The median CyA trough level was an independent and significant risk factor for the development of CAN in children with MCNS receiving moderate-dose CyA.

In this paper we report on a novel fluorescent core skeleton, 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one, which we named Seoul-Fluor, having tunable and predictable photophysical properties. Using a concise and practical one-pot synthetic procedure, a 68-member library of new fluorescent compounds was synthesized with diverse substituents. In Seoul-Fluor, the electronic characteristics of the substituents, as well as their positional changes, have a close correlation with their photophysical properties. The systematic perturbation of electronic densities on the specific positions of Seoul-Fluor, guided with the Hammett constant, allows emission wavelength tunability covering the full color range. On the basis of these observations and a computational analysis, we extracted a simple first-order correlation of photophysical properties with the theoretical calculation and accurately predicted the emission wavelength of Seoul-Fluors through the rational design. In this study, we clearly demonstrate that Seoul-Fluor can provide a powerful gateway for the generation of desired fluorescent probes without the need for a tiresome synthesis and trial-and-error process., (© 2011 American Chemical Society)

Neoplasms and tumorlike lesions that originate from chest wall tissues are uncommon compared with tumors in other parts of the body, and unfamiliarity with these disease entities can cause diagnostic difficulties for radiologists. Furthermore, the imaging features of many of these tumors are nonspecific, particularly those that are locally aggressive. However, a systematic approach based on patient age, clinical history, lesion location, and characteristic imaging findings often helps limit the differential diagnosis. Primary chest wall tumors can be classified as bone or soft-tissue tumors, with the latter being further classified into adipocytic tumors, vascular tumors, peripheral nerve sheath tumors, cutaneous lesions, fibroblastic-myofibroblastic tumors, and so-called fibrohistiocytic tumors, largely based on the 2002 World Health Organization classification. Within each category, it is possible to further limit the differential diagnosis with cross-sectional imaging. Information on specific features (eg, mineralization, fibrosis, hemosiderin deposits) and imaging patterns (eg, the "target sign" and "fascicular sign" seen in neurogenic tumors) can aid in making the diagnosis. Radiologists can achieve a sufficiently specific diagnosis of bone tumors and soft-tissue tumors if typical findings are present., (Copyright © RSNA, 2011.)

The objective of this study was to investigate the ability of E. coli in river sediments to degrade estrogen conjugates. Biodegradation experiments on glucuronide estrogens (E1-GLU, E2-GLU and E3-GLU) using E. coli, non-E. coli bacteria as well as sediment crude extracts were carried out in batch mode. A pure identified E. coli strain (KCTC 2571) was used for comparison of enzyme activity. The results showed that the degradation rate of estrogen conjugates by KCTC 2571 and E. coli isolated from sediments followed a similar trend. Fecal bacteria showed a high ability to deconjugate glucuronided estrogens. Approximately 50% of glucuronide moieties were cleaved within 4 h of contact time in experiments using pure E. coli. The degradation rate was slower in experiments using crude extracts of sediments, and conjugated estrogens were not completely degraded even after 12 h of reaction. These results provide a clear understanding of the fate and behavior of estrogen by bacteria in the environment.

Broad scale monitoring of estrogenic compounds was performed at 19 sampling points throughout the Yeongsan and Seomjin river basins and 5 wastewater treatment plants (WWTPs) adjacent to the Gwangju area, Korea, from December 2005 to August 2007. The concentrations of estrogenic compounds, including estrone (E1), 17β-estradiol (E2), 17α-ethynylestradiol (EE2), bisphenol-A, nonylphenol (NP) and 4-octylphenol (OP), in the samples was measured with gas chromatography/mass spectrometry (GC-MS). In addition, the estrogenic activities throughout the river were investigated using the E-screen assay. Of the six estrogenic chemicals, NP (114.6-336.1 ng L(-1)) and EE2 (0.23-1.90 ng L(-1)) were detected at the highest and lowest levels, respectively in both the river waters and the WWTP effluents. Bisphenol-A showed the largest concentration range, from 7.5 to 335 ng L(-1). The concentrations of E1, E2 and octylphenol ranges were 3.6-69.1, 1.2-10.7, and 2.2-16.9 ng L(-1), respectively. According to the calculated estradiol equivalent concentration (EEQ); however, no estrogenic contribution was observed due to the phenolic compounds in the river waters and effluents. E1 and E2 dominated in both the river water and effluent samples, with contributions to the calculated EEQ of over 79 and 77%, respectively. Conversely, EE2 was rarely detected in the river waters (21%) and effluents (0%). The largest contribution of EE2 to the calculated EEQ was 21% in the river water at S-7. The levels of E1, E2, and EE2 were remarkably decreased in the effluents, indicating that the 5 WWTPs did not contribute to the estrogenic effect of the receiving streams. Overall, the WWTPs did not contributed to the estrogenic activity of the receiving waters, but the livestock industry or wildlife may play an important role in the estrogenic contribution to river water.

Increasing evidence suggests that AR (androgen receptor) acetylation is critical for prostate cancer cell growth. In the present study, we identified Pro-B3 (procyanidin B3) as a specific HAT (histone acetyltransferase) inhibitor. Pro-B3 selectively inhibited the activity of HATs, but not other epigenetic enzymes. Pro-B3 substantially inhibited the p300-mediated AR acetylation, both in vitro and in vivo. Pro-B3 inhibited both p300-dependent and agonist-induced AR transcription. We demonstrate that the p300-mediated AR acetylation is critical for the hormone responsiveness of AR. Interestingly, B3 treatment efficiently enhanced the antagonist activity of flutamide through suppression of p300 HAT activity, demonstrating that relative p300 activity is critical for the antagonist action. Finally, Pro-B3 treatment inhibited acetylation-dependent prostate cell proliferation and expression of cell-cycle control genes, subsequently increasing cell death, indicating the functional importance of AR acetylation for prostate cancer cell growth.

Purpose: The goal of this study was to compare the diagnostic use and safety of endorectal coil (ERC) MRI with those of phased-array coil MRI., Methods: We retrospectively included 91 consecutive patients who had undergone 1.5-T MRI with ERC or with phased-array coil MRI before radical prostatectomy at our institution. We compared 47 patients' phased-array coil MRI and 44 patients' ERC-MRI with histologic findings. We also evaluated adverse events following the MRI procedure., Results: The serum PSA levels ranged from 2.85 to 33.51 ng/mL (10.72 ± 1.9), and the median Gleason score was 7 (range 4-9). The mean interval between diagnostic prostate biopsy and staging MRI was 18.4 days (range 2-37). In assessing organ-confined disease, extracapsular extension and seminal vesicle invasion by MRI, there were no significant differences between ERC-MR group and phased-array coil MR group. The AUC values were 0.671 (95% CI 0.530-0.813) for ERC-MR and 0.657 (95% CI 0.503-0.811) for phased-array coil MR. No significant differences were found between the two groups (p = 0.24). Five patients (11.4%) developed rectal complications after ERC-MRI. However, no complications were found in phased-array coil MRI group., Conclusions: In terms of diagnostic accuracy and comfort of patients, the use of ERC-MRI did not significantly improve the staging of prostate cancer and presented several complications. Therefore, phased-array coil MRI is a better alternative considering comorbidity.