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OBJECTIVE To show experimentally induced renal stone disease and to evaluate secondary inflammatory responses in vivo, and to characterize changes in the expression of Toll-like receptor (TLR) subtypes in this model.

Context: Urothelial carcinoma (UC) is one of the most frequent epithelial tumors worldwide. Aims: We aimed to investigate the protein expressions of caspase-8, p53, murine double minute 2 (mdm2), and p14(ARF) in nonmuscle UCs and to correlate the findings with clinicopathological characteristics. Settings and Design: A total of 50 patients who had pTa and pT1 tumors were analyzed. Subjects and Methods: The protein expressions of caspase-8, p53, mdm2, and p14ARF were analyzed by immunohistochemistry. Statistical Analysis Used: Chi-square test was done using SPSS version 16.0 (SPSS, Inc., Chicago, IL, USA). Results: Cytoplasmic caspase-8 expression was significantly higher in pT1 UCs while nuclear caspase-8 expression was significantly higher in pTa UCs (P = 0.005 and P = 0.011, respectively). Cytoplasmic caspase-8 expression was also higher in high-grade UCs (P = 0.035). The expression of p53, mdm2, and p14ARF was not also related with pathological stage or grade (P > 0.05 for all). The p14ARF expression was related with nuclear caspase-8 expression in most of the patients. Complete agreement among nonmuscle UCs for immunohistochemical expression of p14 and nuclear caspase-8 was seen in 41 cases, and the pairwise kappa agreement value was substantial (kappa = 0.614). The patients who had recurrence were positive for both p53 and mdm2 or either p53 or mdm2 (P = 0.025). Conclusions: These results suggested that the staining pattern of caspase-8 might be helpful for determining of the stages in nonmuscle UC. It was also showed that the expression status of p53 and mdm2 were related with the recurrence.

Purpose: The aim of this study was to investigate and compare the effects of udenafil and mannitol in an experimental renal ischemia-reperfusion (I/R) injury model. Materials and Methods: A total of 64 female Wister Albino rats were used. Right nephrectomy was performed in all groups. In the control group; I/R injury was not performed. In the I/R group; left renal pedicle was clamped for 45 minutes and then underwent 60 minutes and 24 hours of reperfusion. In the mannitol group; 1 mL 20% mannitol was given intravenously 15 minutes before clamping. In the udenafil group; 10-mg/kg udenafil was given orally 1 hour before clamping. Creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, malondialdehyde, neutrophil gelatinase associated lipocalin (NGAL), histological examination and DNA damage (Comet Assay method) levels were compared in tissue, serum and urine samples. Results: Udenafil had a better protective effect than mannitol according to biochemical parameters (Cr, BUN, Cr clearance, and NGAL levels) and histopathological findings when compared with the I/R group. In the Comet sampling analysis no significant difference was detected. Conclusions: Udenafil has a better renoprotective effect than mannitol against I/R injury and this effect supports more functional improvements. Further clinical trials are needed to demonstrate those effects and clinical utility of udenafil for that purpose in humans.

Purpose: Toll-like receptors (TLRs) have an important role in the activation of both innate and adaptive immunity in response to pathogens and endogenous danger signals from damaged or dying cells. The aim of this study was to determine the relationship between urothelial carcinoma (UC) and TLR expression. Basic procedures: Real-time polymerise chain reaction evaluation was made of the messenger RNA expression of TLRs 1-10 in 24 UC samples and 46 nontumoral bladder tissue samples. The levels of proinflammatory cytokines (IL-1 beta, IL-6, and IL-8) in the urine samples were also determined with enzyme-linked immunosorbent assay. Main findings: TLR2-7 and TLR10 expressions were significantly higher in UC than in the control group (P < 0.05 for all comparisons). No concordance was found between matched tumor tissue and urine samples in terms of TLR expression. IL-1 beta, IL-6, and IL-8 levels were significantly higher in urine specimens of patients with UC (P = 0.033, P = 0.001, and P = 0.008, respectively). Principal conclusions: The results of this study demonstrated that the TLR gene expression profiles reflect the heterogeneity within UC. These results might also prompt further investigation to better understand the role of the TLR gene family expression in the tumor progression of UC. (C) 2017 Elsevier Inc. All rights reserved.

OBJECTIVE: We aimed to determine the hot spot mutational frequencies of Enhancer of Zeste homolog 2 (EZH2) and cluster of differentiation 79B (CD79B) genes in a cohort of mature B-cell non-Hodgkin's lymphomas.

Background: Myeloid differentiation primary response 88 (MYD88) is a common adaptor protein that is responsible for signaling from several receptors; mutations in this gene may play a role in the pathogenesis of lymphoma. Aim: We aimed to determine the MYD88 L265P mutation frequency, the level of MYD88 expression, and their associations with clinicopathological parameters in mature B-cell non-Hodgkin lymphomas (NHLs). Methods: A total of 68 patients were included in the study. The presence of the MYD88 L265P mutation was analyzed by real-time polymerase chain reaction and direct sequencing. MYD88 protein expression was evaluated by immunohistochemistry (IHC) using two different scoring systems. Results:MYD88 L265P mutation was present in eight (18.6%) diffuse large B-cell lymphoma (DLBCL) patients. We also observed a significant association between the loss of MYD88 expression and advanced stage in both mature B-cell NHL and DLBCL according to the first IHC scoring systems (p=0.015 and p=0.024, respectively). An association was also seen between MYD88 overexpression and low clinical risk in both mature B-cell NHL and DLBCL according to the second IHC scoring system (p=0.027 and p=0.024, respectively). Conclusions: The L265P mutation may be helpful for understanding the pathogenesis of immune-privileged site-associated DLBCLs. The presence of the mutation, together with its protein overexpression, could also be used as a prognostic marker in advanced stage DLBCLs.

Congenital leukemia is a rare disease. The majority of cases of this disease are acute myelogenous leukemia (AML). Congenital acute lymphoblastic leukemia (ALL) is rare and most often is of B cell lineage. Rarely, some cases have been designated biphenotypic or mixed phenotype acute leukemia (MPAL). Herein, we report a preterm newborn referred to us as a result of the appearance of blue-violaceous dermal nodules on her body at birth. She was a twin and the product of an in vitro fertilization (IVF) pregnancy. Physical examination showed jaundice, hepatosplenomegaly, and peripheral facial nerve palsy in addition to dermal nodules. Bone marrow aspiration showed 40% blasts of lymphoid lineage; skin biopsy and its immunohistochemistry revealed myeloblastic infiltration of the dermis. Cytogenetic analysis (46,XX), fluorescence in situ hybridization (FISH) analysis, and cranial magnetic resonance were normal. The patient was diagnosed with congenital MPAL, and an association between IVF and congenital leukemia was suggested. Copyright (C) 2013, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45 gamma) is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45 gamma methylation, to evaluate the correlation between GADD45 gamma methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. Materials and Methods: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45 gamma methylation status. The GADD45 gamma protein expression was determined by immunohistochemistry. Results: GADD45 gamma methylation was frequent (50.0%) in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041). In contrast, unmethylated GADD45 gamma was associated with nodal involvement as the primary anatomical site (p=0.040). Conclusion: The results of this study show that, in contrast to solid tumors, the frequency of GADD45 gamma methylation is higher and this epigenetic alteration of GADD45 gamma may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45 gamma.

Introduction: There is limited data in the literature about brucellosis related to an intracellular pathogen and anti-tumor necrosis factor alpha (anti-TNF alpha) medication. The aim of this study was to evaluate acute Brucella infections in mice receiving anti-TNF alpha drug treatment. Methodology: Anti-TNF alpha drugs were injected in mice on the first and fifth days of the study, after which the mice were infected with B. melitensis M16 strain. Mice were sacrificed on the fourteenth day after infection. Bacterial loads in the liver and spleen were defined, and histopathological changes were evaluated. Results: Neither the liver nor the spleen showed an increased bacterial load in all anti-TNF alpha drug groups when compared to a non-treated, infected group. The most significant histopathological findings were neutrophil infiltrations in the red pulp of the spleen and apoptotic cells with hepatocellular pleomorphism in the liver. There was no significant difference among the groups in terms of previously reported histopathological findings, such as extramedullary hematopoiesis and granuloma formation. Conclusions: There were no differences in hepatic and splenic bacterial load and granuloma formation, which indicate worsening of the acute Brucella infection in mice; in other words, anti-TNF alpha treatment did not exacerbate the acute Brucella spp. infection in mice.