Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn’s disease

AIM: To assess the prevalence and stability of different antiphospholipid antibodies (APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases (IBD) patients. METHODS: About 458 consecutive patients [Crohn's disease (CD): 271 and ulcerative colitis (UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course (development f complicated disease phenotype and need for surgery), occurrence of thrombotic events, actual state of disease activity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up, (median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls (HC) were tested on individual anti-β2-Glycoprotein-I (anti-β2-GPI IgA/M/G), anti-cardiolipin (ACA IgA/M/G) and anti-phosphatidylserine/prothrombin (anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies (ASCA IgA/G) by enzyme-linked immunosorbent assay (ELISA). In a subgroup of CD (n = 198) and UC patients (n = 103), obtaining consecutive samples over various arbitrary time-points during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally, we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed. RESULTS: Patients with CD had significantly higher prevalence of both ACA (23.4%) and anti-PS/PT (20.4%) antibodies than UC (4.8%, P < 0.0001 and 10.2%, P = 0.004) and HC (2.9%, P < 0.0001 and 15.5%, P = NS). No difference was found for the prevalence of anti-β2-GPI between different groups (7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients. Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes. Changes in antibody status were more remarkable in CD than UC (ACA IgA: 49.9% vs 23.3% and ACA IgG: 21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis. CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However, presence of different APLAs were not associated with the clinical phenotype or disease course

Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary

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Epigenetic mechanisms in virus-induced tumorigenesis

About 15–20% of human cancers worldwide have viral etiology. Emerging data clearly indicate that several human DNA and RNA viruses, such as human papillomavirus, Epstein–Barr virus, Kaposi’s sarcoma-associated herpesvirus, hepatitis B virus, hepatitis C virus, and human T-cell lymphotropic virus, contribute to cancer development. Human tumor-associated viruses have evolved multiple molecular mechanisms to disrupt specific cellular pathways to facilitate aberrant replication. Although oncogenic viruses belong to different families, their strategies in human cancer development show many similarities and involve viral-encoded oncoproteins targeting the key cellular proteins that regulate cell growth. Recent studies show that virus and host interactions also occur at the epigenetic level. In this review, we summarize the published information related to the interactions between viral proteins and epigenetic machinery which lead to alterations in the epigenetic landscape of the cell contributing to carcinogenesis

Knudsen layer theory for high-order lattice Boltzmann models

A Knudsen layer theory is presented within the framework of a high-order lattice Boltzmann model obtained from the fourth-order Gauss-Hermite quadrature. The Kramers problem is analyzed in detail. We employ a multi-relaxation collision operator which is shown to permit a variable layer width. Computer simulations are performed which give excellent agreement with the theoretical derivations. Good qualitative agreement is achieved with the accurate numerical solution of the Boltzmann equation for hard sphere molecules. Our theoretical result clearly indicates that the lattice Boltzmann models with high symmetric velocity sets naturally develop to physically relevant Knudsen layers due to the discrete ordinate origin of the method

Lattice boltzmann model as an innovative method for microfluidics

The lattice Boltzmann model is an innovative method to simulate gaseous or liquid flows. It successfully fills the gap between the macroscopic description, the Navier-Stokes equation, and particle based methods, such as the direct simulation of Monte-Carlo. In the last years, the lattice Boltzmann model has attracted increasing attention in modeling flows in microfluidic devices. This area has developed rapidly. Microelectromechanical systems (MEMS), gaseous sensors, lab-on-chips produce significant grow in various areas of engineering and technology. In this chapter, we give an overview of the lattice Boltzmann method and its key concepts. We review recent developments related to the field of microflows and microfluidics. Particular attention is paid for non-continuum behaviours observed at the micro-scale, such as the slip and jump of macroscopic variables in a micro-device. Finally, we provide further ideas and directions which can serve as targets of future developments. Beyond the lattice Boltzmann model, these ideas can stimulate progress and investment in applications and technology. © 2010 Nova Science Publishers, Inc. All rights reserved

Flow cytometric assay of phagocytic activity of human neutrophils and monocytes in whole blood by neutral red uptake

In a new, simple, and fast flow-cytometricmethod for the simultaneous measurement of phagocyticactivity of human neutrophils and monocytes inwhole blood, the fluorescence capability of the wellknownvital stain, neutral red was used. The incubationof 0.5 ml heparinized human blood with the phagocyticstimulus of zymosan dose- and time-dependently increasedthe percentage and the red fluorescence intensityof both neutrophils (4.3 _ 1.2 times) and monocytes(2.7_+0.7 times) measured cytofluorimetrically. Decreaseduptake of neutral red was observed in a patientwith phagocytic disorder, based upon impaired engulfmentof particles and production of reactive oxygenspecies. In a patient with chronic granulomatosis, however,no decrease of neutral red uptake was measured.Platelet activating factor and phorbol myristate acetatewere also able to increase the uptake of neutral red byboth monocytes and neutrophils, but to a lesser extentthan zymosan. The advantage of this method is the possibilityfor the simultaneous measurement of phagocyticactivities of monocytes and neutrophils stimulated byeither particles or soluble activators. This method issuitable for the selective measurement of activationprocesses not related to the production of free radicalsin the phagocytes