Isolation and1H-NMR spectroscopic identification of the glucose-containing lipid-linked precursor oligosaccharide ofN-linked carbohydrate chains

The lipid-linked precursor ofN-type glycoprotein oligosaccharides was isolated from porcine thyroid microsomes after in cubation with UDP[³H] Glucose. The carbohydrate was released from dolichol pyrophosphate by mild acid hydrolysis, purified by gel filtration and characterized by 500-MHz¹H-NMR spectroscopy in combination with enzymatic degradation. The parent oligosaccharide was found to be Glc₃Man₉Glc-NAc₂. The three glucose residues are present in the linear sequence Glcα1-2Glα1-3 Glc, the latter being α(1-3)-linked to one of the mannose residues. In order to establish the branch location of the triglucosyl unit, the parent compound was digested with jack-bean α-mannosidase. The oligosaccharide product was purified by gel filtration, and identified by¹H-NMR as Glc₃Man₅GlcNAc₂ lacking the mannose residues A, D₂, B and D₃. Therefore, the structure of the precursor oligosaccharide is as follows: $$\begin{gathered} c b a D_1 C 4 \hfill \\ Glc\alpha 1 - 2Glc\alpha 1 - 3Glc\alpha 1 - 3Man\alpha 1 - 2Man\alpha 1 - 2Man\alpha 1 \hfill \\ 3 \swarrow 3 2 1 \hfill \\ Man\alpha 1 - 2Man\alpha 1 Man\beta 1 - 4GlcNAc\beta 1 - 4GlcNAc \hfill \\ D_{2 } A 3 6 \hfill \\ Man\alpha 1 \hfill \\ 6 \hfill \\ Man\alpha 1 - 2Man\alpha 1 \nwarrow 4 \hfill \\ D_3 B \hfill \\ \end{gathered} $$      

Bacterial lipopolysaccharide and gamma interferon induce transcription of beta interferon mRNA and interferon secretion in murine macrophages

Bacterial lipopolysaccharide (LPS) induces interferon (IFN) secretion and an antiviral state in murine peritoneal macrophages (PM). These cells secrete predominantly IFN-beta, as shown by neutralization assays with monoclonal antibodies. Secretion of IFN-beta is also induced in PM by IFN-gamma. LPS and IFN-gamma synergistically stimulated PM to produce IFN in amounts almost comparable to those induced by infection with Newcastle disease virus. Low levels of IFN-beta mRNA can be detected in freshly harvested PM by hybridization assays. The accumulation of this mRNA is markedly increased in PM treated with LPS or IFN-gamma, and it is further enhanced in the presence of the inhibitor of protein synthesis, cycloheximide. Similar studies were carried out on the RAW 264.7 line of transformed macrophages. These cells are induced to secrete IFN-beta by LPS but not by IFN-gamma, suggesting that this cytokine may elicit such specific response only in PM. IFN-beta mRNA is undetectable in untreated RAW 264.7 cells, and accumulation of this mRNA is induced by LPS but not by IFN-gamma. The secretion of IFN induced by these agents in PM and by LPS in RAW 264.7 cells and the corresponding accumulation of IFN-beta mRNA are blocked by an inhibitor of protein kinase C, staurosporine. The activity of this kinase is apparently necessary to stimulate accumulation of IFN-beta mRNA. The induction of IFN-beta by IFN-gamma appears to be a characteristic response of PM and may be at least in part responsible for the resistance of these cells to viral infections.     

Suture materials and other factors associated with tissue reactivity, infection, and wound dehiscence among plastic surgery outpatients

The most common complications in plastic surgery are tissue reactivity, infections, and wound dehiscence. In the literature, there are only a few studies with sample sizes large enough and methods of statistical analysis appropriate for evaluating the role of suture materials in inducing such complications. In the 1000 plastic surgery outpatients in this study, the association of different suture materials, individual patient characteristics, surgeon skill, and wound site and length with postoperative wound complications (i.e., tissue reactivity, infection rate, and wound dehiscence) were investigated. No substantial differences were found between the different suture materials and suturing techniques. A moderate increase in the risk of tissue reactivity for silk and polyglactin 910 and a protective effect of thinner internal sutures were observed. In multivariate analysis, such differences were not statistically significant. Male sex [odds ratio (OR), 1.7; 95 percent confidence interval (CI), 1.06 to 2.72] and older age (OR, 2.34; 95 percent CI, 1.36 to 4.05) were found to be the most important risk factors for tissue reactivity and infection rate (male sex: OR, 5.1; 95 percent CI, 1.7 to 15.9; older age: OR, 5.6; 95 percent CI, 1.9 to 16), whereas younger age was associated with an increased risk of dehiscence (OR, 3.06; 95 percent CI, 1.41 to 6.65). Wounds on the lower limbs showed a lower risk of tissue reactivity and wounds on the back a higher risk of dehiscence. Wound length was associated with the risk of tissue reactivity in one-layer sutures (OR, 2.92; 95 percent CI, 1.51 to 5.65). An increased risk of both tissue reactivity (OR, 1.53; 95 percent CI, 1.03 to 2.27) and dehiscence (OR, 2.44; 95 percent CI, 1.1 to 5.43) was observed for operations performed by less-experienced surgeons. Rather than factors related to suture materials and different surgical techniques, and with the exception of surgeon experience, general characteristics of the patients (i.e., sex and age) and of the wounds (i.e., length and site) seemed to be primarily responsible for local wound complications.     

A New 4D Trajectory-Based Approach Unveils Abnormal LV Revolution Dynamics in Hypertrophic Cardiomyopathy

The assessment of left ventricular shape changes during cardiac revolution may be a new step in clinical cardiology to ease early diagnosis and treatment. To quantify these changes, only point registration was adopted and neither Generalized Procrustes Analysis nor Principal Component Analysis were applied as we did previously to study a group of healthy subjects. Here, we extend to patients affected by hypertrophic cardiomyopathy the original approach and preliminarily include genotype positive/phenotype negative individuals to explore the potential that incumbent pathology might also be detected. Using 3D Speckle Tracking Echocardiography, we recorded left ventricular shape of 48 healthy subjects, 24 patients affected by hypertrophic cardiomyopathy and 3 genotype positive/phenotype negative individuals. We then applied Generalized Procrustes Analysis and Principal Component Analysis and inter-individual differences were cleaned by Parallel Transport performed on the tangent space, along the horizontal geodesic, between the per-subject consensuses and the grand mean. Endocardial and epicardial layers were evaluated separately, different from many ecocardiographic applications. Under a common Principal Component Analysis, we then evaluated left ventricle morphological changes (at both layers) explained by first Principal Component scores. Trajectories’ shape and orientation were investigated and contrasted. Logistic regression and Receiver Operating Characteristic curves were used to compare these morphometric indicators with traditional 3D Speckle Tracking Echocardiography global parameters. Geometric morphometrics indicators performed better than 3D Speckle Tracking Echocardiography global parameters in recognizing pathology both in systole and diastole. Genotype positive/phenotype negative individuals clustered with patients affected by hypertrophic cardiomyopathy during diastole, suggesting that incumbent pathology may indeed be foreseen by these methods. Left ventricle deformation in patients affected by hypertrophic cardiomyopathy compared to healthy subjects may be assessed by modern shape analysis better than by traditional 3D Speckle Tracking Echocardiography global parameters. Hypertrophic cardiomyopathy pathophysiology was unveiled in a new manner whereby also diastolic phase abnormalities are evident which is more difficult to investigate by traditional ecocardiographic techniques.     

Increased expression of costimulatory markers CD134 and CD80 on interleukin-17 producing T cells in patients with systemic lupus erythematosus

Introduction  

There is growing evidence that interleukin 17 (IL-17) producing T cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies showed that increased percentages of T-cell subsets expressing the costimulatory molecules CD80 and CD134 are associated with disease activity and renal involvement in SLE. The aim of this study was to investigate the distribution and phenotypical characteristics of IL-17 producing T-cells in SLE, in particular in patients with lupus nephritis, with emphasis on the expression of CD80 and CD134.     

Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study

Introduction  

Identifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-α) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-α blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-α blocking therapy in AS patients in daily clinical practice.     

Advanced glycation endproducts are increased in rheumatoid arthritis patients with controlled disease

Introduction  

Advanced glycation end products (AGEs) are produced and can accumulate during chronic inflammation, as might be present in patients with rheumatoid arthritis (RA). AGEs are involved in the development of cardiovascular disease. The aim of this study is to evaluate whether AGEs are increased in patients with long-standing RA and whether AGE accumulation is related to disease activity, disease severity and measures of (premature) atherosclerosis, such as endothelial activation, endothelial dysfunction and intima media thickness (IMT).     

Expression of collier in the premandibular segment of myriapods: support for the traditional Atelocerata concept or a case of convergence?

Background  

A recent study on expression and function of the ortholog of the Drosophila collier (col) gene in various arthropods including insects, crustaceans and chelicerates suggested a de novo function of col in the development of the appendage-less intercalary segment of insects. However, this assumption was made on the background of the now widely-accepted Pancrustacea hypothesis that hexapods represent an in-group of the crustaceans. It was therefore assumed that the expression of col in myriapods would reflect the ancestral state like in crustaceans and chelicerates, i.e. absence from the premandibular/intercalary segment and hence no function in its formation.