Effects of ageing, surface sialic acid and glycopeptides of erythrocytes on auto-rosettes in man.

Human red blood cells can bind in vitro to autologous peripheral blood lymphocytes forming auto-rosettes. The percentage of rosett-forming cells (A-RFC) depends on erythrocyte ageing in vivo. Old untreated cells given an A-RFC percentage lower as compared with the young ones. The same age groups of cells treated with neuraminidase show a parallel increase of A-RFC as compared with untreated cells. No significant difference is found between young and old cells with high concentrations of neuraminidase. The rosetting formation is inhibited by the pre-treatment of lymphocytes with erythrocyte glycopeptides released by trypsin. This suggests that auto-rosetting is mediated by erythrocyte surface glycopeptides in which sialic acid plays a role directly or not.     

A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity

IL-1F7 was discovered in expressed sequence tag databases as a member of the increasing family of proteins sharing sequence homology to IL-1alpha/beta, IL-1Ra, and IL-18. In the present study using immunohistochemical staining, IL-1F7 was localized in human peripheral monocytic cells, suggesting its role in immune regulation. Recombinant human IL-1F7b was shown to bind to the IL-18Ralpha but without IL-18 agonistic or antagonistic function. Using chemical cross-linking, we observed that, unlike IL-18, IL-1F7b fails to recruit the IL-18Rbeta chain to form a functionally active, ternary complex with the IL-18Ralpha chain. IL-1F7b shares two conserved amino acids with IL-18 (Glu-35 and Lys-124), which participate in the interaction of IL-18 with the IL-18Ralpha chain as well as the IL-18-binding protein (IL-18BP), a secreted protein that neutralizes IL-18 activity. In testing whether IL-1F7b interacts with IL-18BP, we unexpectedly observed that IL-1F7b enhanced the ability of IL-18BP to inhibit IL-18-induced IFNgamma by 25-30% in a human natural killer cell line. This effect was observed primarily at limiting concentrations of IL-18BP (3.12-12.5 ng/ml) and at a 50- to 100-fold molar excess of IL-1F7b. Similar results were obtained by using isolated human peripheral blood mononuclear cells. To study the molecular basis of this effect we performed binding studies of IL-1F7b and IL-18BP. After cross-linking, a high molecular weight complex consisting of IL-1F7b and IL-18BP was observed on SDS/PAGE. We propose that after binding to IL-18BP, IL-1F7b forms a complex with IL-18Rbeta, depriving the beta-chain of forming a functional receptor complex with IL-18Ralpha and thus inhibiting IL-18 activity.     

RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3

OBJECTIVE: To assess the expression of Toll-like receptor 3 (TLR-3) protein in synovial tissues and cultured synovial fibroblasts obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate the consequences of stimulation of cultured synovial fibroblasts with TLR-3 ligands. METHODS: TLR-3 expression in synovial tissues was determined by immunohistochemistry and immunofluorescence, and expression in cultured RA synovial fibroblasts (RASFs) was determined by fluorescence-activated cell sorting and real-time polymerase chain reaction techniques. TLR-3 signaling was assessed by incubating RASFs with poly(I-C), lipopolysaccharide, palmitoyl-3-cysteine-serine-lysine-4, or necrotic synovial fluid cells from RA patients in the presence or absence of hydroxychloroquine or Benzonase. Subsequent determination of interferon-beta (IFNbeta), CXCL10, CCL5, and interleukin-6 (IL-6) protein production in the culture supernatants was performed by enzyme-linked immunosorbent assays. RESULTS: TLR-3 protein expression was found to be higher in RA synovial tissues than in OA synovial tissues. TLR-3 expression was localized predominantly in the synovial lining, with a majority of the TLR-3-expressing cells coexpressing fibroblast markers. Stimulation of cultured RASFs with the TLR-3 ligand poly(I-C) resulted in the production of high levels of IFNbeta, CXCL10, CCL5, and IL-6 protein. Similarly, coincubation of RASFs with necrotic synovial fluid cells from patients with RA resulted in up-regulation of these cytokines and chemokines in a TLR-3-dependent manner. CONCLUSION: Our findings demonstrate the expression of TLR-3 in RA synovial tissue and the activation of RASFs in vitro by the TLR-3 ligand poly(I-C) as well as by necrotic RA synovial fluid cells, and indicate that RNA released from necrotic cells might act as an endogenous TLR-3 ligand for the stimulation of proinflammatory gene expression in RASFs.     

Relaxation versus fractionation as hypnotic deepening: do they differ in physiological changes?

After rapid hypnotic induction, 12 healthy volunteers underwent hypnotic deepening with relaxation or with fractionation (without relaxation) in a random latin-square protocol. Electroencephalographic occipital alpha activity was measured, low-resolution brain electromagnetic tomography was performed, and hemodynamics (stroke volume, heart rate, cardiac output, mean arterial blood pressure, forearm arterial flow and resistance) were monitored in basal conditions and after deepening. After relaxation, both forearm flow (-18%) and blood pressure (-4%) decreased; forearm resistance remained unchanged. After fractionation, a forearm flow decrease comparable to that recorded after relaxation was observed, but blood pressure remained unchanged, leading to an increase of forearm resistance (+51%). Central hemodynamics did not change. Alpha activity increased in the precuneus after fractionation only. In conclusion, both relaxation and fractionation have vasoconstrictor effects, but fractionation is also associated with an increase in peripheral resistance.     

Increased numbers of sodium channels form along demyelinated axons

Sodium channels, which are largely localized to the nodes of Ranvier in myelinated axons, appear to form new distributions along demyelinated axons. In this study a sensitive radioimmunoassay (RIA) was used to examine the changes in the total number of sodium channels that occur in nerves experimentally demyelinated in vivo with doxorubicin (adriamycin). The results clearly illustrate the development of an increased number of sodium channels during demyelination, suggesting that this process is associated with the formation of new sodium channels.     

The effect of cigarette smoking on the risk of preeclampsia and gestational hypertension

This case-control study assessed the relation of cigarette smoking during pregnancy to the risk of preeclampsia and gestational hypertension. All subjects were primiparous women without a history of high blood pressure who gave birth in Quebec City or Montreal, Canada, hospitals between 1984 and 1986. Cases (172 women with preeclampsia and 251 with gestational hypertension) and 505 controls were interviewed at the hospital after delivery. Adjusted relative risks were estimated by polychotomous logistic regression. Compared with women who had never smoked, women who were smokers at the onset of pregnancy had a reduced risk of preeclampsia (relative risk = 0.51, 95% confidence interval 0.34-0.77). Relative risks of preeclampsia decreased with increases in the number of cigarettes smoked daily at the onset of pregnancy: Relative risks among smokers of less than 11, 11-20, and more than 20 cigarettes per day were 0.79, 0.56, and 0.38, respectively (test for trend: p = 0.0002). The protective effect of smoking on preeclampsia was stronger for women who continued to smoke after 20 weeks of pregnancy. While smoking tended to reduce the risk of gestational hypertension, this effect was less evident than that for preeclampsia. Relative risks varied little with severity of disease as based on gestational age at the onset of hypertension, maximal blood pressure and, for preeclampsia, amount of proteinuria. The reduction in mean birth weight attributable to smoking during pregnancy was similar among cases and controls. Nicotine inhibition of thromboxane A2 production might explain the decreased risk of pregnancy-induced hypertension among smokers. Despite these findings, the harmful consequences of smoking on pregnancy outcome outweigh its protective effect against pregnancy-induced hypertension.     

Clinical evaluation of nanofill and nanohybrid composite in Class I restorations: a 12-month randomized trial

This randomized trial evaluated the 12-month clinical performance of nanofill, a nanohybrid, and a microhybrid composite in restorations in occlusal cavities of posterior teeth. This study utilized 41 patients, each of whom had three molars affected by primary caries or the need to replace restorations. All restorations were performed in accordance with the manufacturer's recommendations and evaluated in accordance with U.S. Public Health Service-modified criteria. Based on the results of the present study, the material investigated demonstrated acceptable clinical performance after 12 months of clinical service. Long-term re-evaluations are necessary for a more detailed analysis of these composites.