Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies

Introduction

Anti-Jo-1 and anti-Ro52 autoantibodies are common in patients with myositis, but the mechanisms behind their production are not known. Survival of autoantibody-producing cells is dependent on B-cell-activating factor of the tumour necrosis factor family (BAFF). BAFF levels are elevated in serum of anti-Jo-1-positive myositis patients and are influenced by type-I interferon (IFN). IFN-producing cells and BAFF mRNA expression are present in myositis muscle. We investigated expression of the receptors for BAFF in muscle tissue in relation to anti-Jo-1 and anti-Ro52/anti-Ro60 autoantibodies and type-I IFN markers.

Methods

Muscle biopsies from 23 patients with myositis selected based on autoantibody profile and 7 healthy controls were investigated for expression of BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Nineteen samples were assessed for plasma (CD138) and B-cell (CD19) markers. The numbers of positive cells per area were compared with the expression of plasmacytoid dendritic cell (pDC) marker blood dendritic cell antigen-2 (BDCA-2) and IFNα/β-inducible myxovirus resistance-1 protein (MX-1).

Results

BAFF-R, BCMA and TACI were expressed in five, seven and seven patients, respectively, and more frequently in anti-Jo-1-positive and/or anti-Ro52/anti-Ro60-positive patients compared to controls and to patients without these autoantibodies (P = BAFF-R: 0.007, BCMA: 0.03 and TACI: 0.07). A local association of receptors with B and plasma cells was confirmed by confocal microscopy. The numbers of CD138-positive and BCMA-positive cells were correlated (r = 0.79; P = 0.001). Expression of BDCA-2 correlated with numbers of CD138-positive cells and marginally with BCMA-positive cells (r = 0.54 and 0.42, respectively; P = 0.04 and 0.06, respectively). There was a borderline correlation between the numbers of positively stained TACI cells and MX-1 areas (r = 0.38, P = 0.08).

Conclusions

The expression pattern of receptors for BAFF on B and plasma cells in muscle suggests a local role for BAFF in autoantibody production in muscle tissues of patients with myositis who have anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies. BAFF production could be influenced by type-I IFN produced by pDCs. Thus, B-cell-related molecular pathways may participate in the pathogenesis of myositis in this subset of patients.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0454-8) contains supplementary material, which is available to authorized users.     

The interrelations of radiologic findings and mechanical ventilation in community acquired pneumonia patients admitted to the intensive care unit: a multicentre retrospective study

Background

Burkholderia cepacia complex (BCC) bacteria are highly virulent, typically multidrug-resistant, opportunistic pathogens in cystic fibrosis (CF) patients and other immunocompromised individuals. B. vietnamiensis is more often susceptible to aminoglycosides than other BCC species, and strains acquire aminoglycoside resistance during chronic CF infection and under tobramycin and azithromycin exposure in vitro, apparently from gain of antimicrobial efflux as determined through pump inhibition. The aims of the present study were to determine if oxidative stress could also induce aminoglycoside resistance and provide further observations in support of a role for antimicrobial efflux in aminoglycoside resistance in B. vietnamiensis.

Findings

Here we identified hydrogen peroxide as an additional aminoglycoside resistance inducing agent in B. vietnamiensis. After antibiotic and hydrogen peroxide exposure, isolates accumulated significantly less [³H] gentamicin than the susceptible isolate from which they were derived. Strains that acquired aminoglycoside resistance during infection and after exposure to tobramycin or azithromycin overexpressed a putative resistance-nodulation-division (RND) transporter gene, amrB. Missense mutations in the repressor of amrB, amrR, were identified in isolates that acquired resistance during infection, and not in those generated in vitro.

Conclusions

These data identify oxidative stress as an inducer of aminoglycoside resistance in B. vietnamiensis and further suggest that active efflux via a RND efflux system impairs aminoglycoside accumulation in clinical B. vietnamiensis strains that have acquired aminoglycoside resistance, and in those exposed to tobramycin and azithromycin, but not hydrogen peroxide, in vitro. Furthermore, the repressor AmrR is likely just one regulator of the putative AmrAB-OprM efflux system in B. vietnamiensis.     

Accumulation of weathered pp'-DDE in xylem sap of grafted watermelon

Movement of weathered p,p'-dichlorodiphenyldichloroethane (p,p'-DDE) from contaminated soil to the rhizosphere pore water to the xylem sap of grafted watermelon was studied under green house conditions. p,p'-DDE concentrations in pore water and xylem sap was compared in intact plants, homografted, and compatible heterografts of Cucurbita pepo spp. pepo and Citrullus lanatus plants. An average p,p'-DDE concentrations in pore water of contaminated soil ranged from 0.36 microg/L to 0.55 microg/L and there were no statistically significant among the cultivars. Conversely, the xylem sap p,p'-DDE concentration of heterografted watermelon having a zucchini rootstock and watermelon scion was 71 microg/L and it was greater than intact watermelon plants (0.49 microg/L) but less than that of intact plants of zucchini (141 microg/L). Homografting showed no effect on xylem sap p,p'-DDE concentrations of the identical cultivars. The bio-concentration factors (BCFs) which is an average p,p'-DDE concentration in xylem sap over average p,p'-DDE in pore water were 344, 325, 197, 1.28, and 0.89 for intact plant of zucchini, homografted zucchini, heterografted watermelon, homografted watermelon, and intact plant of watermelon, respectively. Xylem sap p,p'-DDE concentrations of the heterografted watermelon plants were clearly influenced by plant phylogeny and enhanced by the zucchini rootstock compared to intact watermelon plants.     

The effects of heat treatment on physical properties and surface roughness of red-bud maple (Acer trautvetteri Medw.) wood

Heat treatment is often used to improve the dimensional stability of wood. In this study, the effects of heat treatment on physical properties and surface roughness of red-bud maple (Acer trautvetteri Medw.) wood were examined. Samples obtained from Düzce Forest Enterprises, Turkey, were subjected to heat treatment at varying temperatures and durations. The physical properties of heat-treated samples were compared against controls in order to determine their; oven-dry density, air-dry density, and swelling properties. A stylus method was employed to evaluate the surface characteristics of the samples. Roughness measurements, using the stylus method, were made in the direction perpendicular to the fiber. Three main roughness parameters; mean arithmetic deviation of profile (Ra), mean peak-to-valley height (Rz), and maximum roughness (Rmax) obtained from the surface of wood, were used to evaluate the effect of heat treatment on the surface characteristics of the specimens. Significant differences were determined (p>0.05) between surface roughness parameters (Ra, Rz, Rmax) at three different temperatures and three periods of heat treatment. The results showed that the values of density, swelling and surface roughness decreased with increasing temperature treatment and treatment times. Red-bud maple wood could be utilized successfully by applying proper heat treatment techniques without any losses in investigated parameters. This is vital in areas, such as window frames, where working stability and surface smoothness are important factors.     

Effect of Lycopene Application in Rats with Experimental Diabetes Using Lipoprotein, Paraoxonase and Cytokines

This study was conducted with the purpose of researching the effect of lycopene application on lipoprotein, paraoxonase (PON) and cytokines that are projected to be used in the diagnosis and treatment of diabetes by making experimental diabetes. At the end of a 1-month trial period, under ether anesthesia with jelly tubes, blood samples were taken from rat hearts. Blood samples were centrifuged and serum was obtained. From the serum samples, HbA_1c, paraoxonase activity, lipoprotein levels and cytokines were determined. HbA_1c levels and PON activity were found to be p < 0.001. At the triglyceride level, with regard to the control group, in all the groups a significant rise occurred (p ≤ 0.001). At the cholesterol level, with regard to the control group, a decline was observed in the other groups (p < 0.05). At the VLDL level, with regard to the control group, a significant rise was observed in the other groups (p < 0.05). At the HDL (p < 0.001) and LDL (p < 0.05) levels, with regard to the control group, a significant decline was observed in the other groups. At the TNF-α, IL-2, IL-6 and IL-10 levels no difference was found (p > 0.05). Experimental diabetes models have an important place in analyzing diabetes complications and determining treatment approaches.     

An in-vitro investigation of the effect of perfluorooctane sulphonate on cell lines of embryonic origin

Fluorinated organic compounds, such as perfluorooctane sulfonate, are stable chemicals with a wide range of industrial applications. The potential toxicity of perfluorooctane sulfonate is not well characterized, and even less known are the mechanisms underlying its toxic effects. Perfluorooctane sulfonate change of inner mitochondrial membrane permeability has been implicated as a potential mechanism of toxicity. In this study, we research that perfluorooctane sulfonate effects the expression of Apaf1 and Caspase3 genes in the amnion and fetal lung cell line that initiate the cells to undergo apoptosis. The expression of Caspase3 and Apaf1 was determined by using quantitative RT-PCR. In the study there is significant increase in expression of Caspase3 and Apaf1 in amnion and fetal lung cell line exposed to high dose (p < 0.001, p = 0.004). Also there is significant increase in cell lines exposed for a long period of time to perfluorooctane sulfonate (p = 0.001). But no significant increase was seen in the low doses and exposed for a short period of time. In conclusion, apoptotic gene expression is increase in cells exposed perfluorooctane sulfonate by dose dependent manner was determined. So this work is the first study examines the apoptotic effects of perfluorooctane sulfonate in human embryonic cells it will lead the way to the other topical studies.     

LC-HRMS Profiling and Phenolic Content,Cholinesterase, and Antioxidant Activities of Terminalia citrina

Terminalia citrina (T. citrina) belongs to the Combretaceae family and is included in the class of medicinal plants in tropical countries such as Bangladesh, Myanmar, and India. The antioxidant activities of lyophilized water (WTE) and alcohol extracts (ETE) of T. citrina fruits, their phenolic content by LC-HRMS, and their effects on cholinesterases (ChEs; AChE, acetylcholinesterase, and BChE, butyrylcholinesterase) were investigated. Especially ten different analytical methods were applied to determine the antioxidant capacity. Compared with similar studies for natural products in the literature, it was determined that both WTE and ETE exhibited strong antioxidant capacity. Syringe and ellagic acids were higher than other acids in ETE and WTE. IC₅₀ values for ETE and WTE in DPPH radical and ABTS⋅⁺ scavenging activities were calculated as 1.69–1.68 μg mL⁻¹ and 6.79–5.78 μg mL⁻¹, respectively. The results of the biological investigations showed that ETE and WTE had an inhibition effect against ChEs, with IC₅₀ values of 94.87 and 130.90 mg mL⁻¹ for AChE and 262.55 and 279.70 mg mL⁻¹ for BChE, respectively. These findings indicate that with the prominence of herbal treatments, T. citrina plant may guide the literature in treating Alzheimer's Disease, preventing oxidative damage, and mitochondrial dysfunction.     

Microcarrier cultivation of bovine aortic endothelial cells in spinner vessels and a membrane stirred bioreactor

Primary bovine aortic endothelial cells were cultivated in serum supplemented medium without any additional growth factors. The anchorage dependent cells were propagated on Dormacell^® microcarriers with covalently bound dimeric DEAE-groups at the surface of the dextrane beads. Cultivations were performed in 200 ml spinner cultures containing 1 g l^–1 to 3 g l^–1 of microcarriers. Out of five types of Dormacell^® microcarriers with different ion exchange capacities ranging from 0.30 up to 0.65 meq g^–1, corresponding to nitrogen contents from 1.2% to 2.9%, respectively, optimal attachment and growth of endothelial cells were obtained with beads of highest nitrogen content (2.9%). Cells were seeded withca. 5 viable cells per microcarrier being sufficient to achieve fully confluent microcarriers after 4 to 5 days. Glucose concentrations decreased from 21 mM to uppermost half of the original concentrations. 4 mM glutamine was rapidly consumed and virtually exhausted after the cells reached confluency. Lactate concentrations raised to a maximum of 7 mM in spinner cultures, but was found to be reutilized in the stationary phase after glutamine limitation occurred. Serine was found to be the second most prominent amino acid being almost exhausted at confluency whereas alanine was produced in noteworthy amounts. Considerable decrease was determined for threonine, lysine and arginine; low consumption rates were observed for leucine, phenylalanine and methionine. All other amino acids did not alter significantly throughout cultivation. These data support that bovine aortic endothelial cells are capable to utilize glucose and glutamine as well as lactic acid (after glutamine exhaustion) as energy and/or carbon source. Finally, batch cultures in a 2 liter membrane stirred bioreactor with bubble-free aeration were performed to produce large quantities of endothelial cells using microcarrier concentrations of 3 g l^–1.Abbreviations BAE cells bovine aortic endothelial cells - NCS newborn calf serum - PBS phosphate buffered saline     

The effects of vitamins and selenium mixture against brain tissue induced by d‐galactosamine

Brain damage is a major complication of fulminant hepatic failure. d ‐Galactosamine (d ‐GalN)‐induced liver toxicity causes damage to brain. The effects of vitamins and selenium mixture against d ‐GalN stimulated brain injury were investigated in this study. Sprague‐Dawley female rats aged 2.0‐2.5 months were used for the study. The rats were divided into four categories. A 0.9% NaCl solution was intraperitoneally given to the experimental rats in the first group. Using gavage technique, the second group of animals were subjected to a formulation consisting of 100 mg·kg^?1·day^?1 vitamin C, 15 mg·kg^?1·day^?1 of β‐carotene, 100 mg·kg^?1·day^?1 of α‐tocopherol in addition to 0.2 mg·kg^?1·day^?1 of sodium selenate for 3 days. The third group was given a single dose of d ‐GalN hydrochloride at the concentration of 500 mg·kg^?1 through a saline injection. The final group was given similar concentrations of both the antioxidant combination and d ‐GalN. Tissue samples were collected under ether anesthesia. The rats treated with d ‐GalN showed brain damage; increased myeloperoxidase, catalase, glutathione peroxidase, glutathione‐S‐transferase, lactate dehydrogenase, and superoxide dismutase activities; and decreased glutathione levels. Treatment with vitamins and selenium combination resulted in alleviation of these alterations in the rats. These findings suggest that administration of the vitamins and selenium combination suppresses oxidative stress and protects brain cells from injury induced by d ‐GalN.