Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases

BACKGROUND: Inflammatory lung diseases are a major morbidity factor in children. Therefore, novel strategies for early detection of inflammatory lung diseases are of high interest. Bacterial lipopolysaccharide (LPS) is recognized via Toll-like receptors and CD14. CD14 exists as a soluble (sCD14) and membrane-associated (mCD14) protein, present on the surface of leukocytes. Previous studies suggest sCD14 as potential marker for inflammatory diseases, but their potential role in pediatric lung diseases remained elusive. Therefore, we examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases. METHODS: sCD14 levels were quantified in serum and bronchoalveolar lavage fluid (BALF) of children with infective (pneumonia, cystic fibrosis, CF) and non-infective (asthma) inflammatory lung diseases and healthy control subjects by ELISA. Membrane CD14 expression levels on monocytes in peripheral blood and on alveolar macrophages in BALF were quantified by flow cytometry. In vitro studies were performed to investigate which factors regulate sCD14 release and mCD14 expression. RESULTS: sCD14 serum levels were specifically increased in serum of children with pneumonia compared to CF, asthma and control subjects. In vitro, CpG induced the release of sCD14 levels in a protease-independent manner, whereas LPS-mediated mCD14 shedding was prevented by serine protease inhibition. CONCLUSIONS: This study demonstrates for the first time the expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases and suggests sCD14 as potential marker for pneumonia in children.

The Influence of PRP on Early Bone Formation in Membrane Protected Defects. A Histological and Histomorphometric Study in the Rabbit Calvaria

Platelet rich plasma (PRP) has been proposed to be a useful adjunct to bone grafting.

Clinical and Histological Evaluation of a Granular Bovine Bone Biomaterial Used as an Adjunct to Guided Tissue Regeneration With a Bioresorbable Bovine Pericardium Collagen Membrane in the Treatment of Intrabony Periodontal Defects

The aim of the present study is to evaluate the clinical and histologic healing of deep intrabony defects treated with guided tissue regeneration (GTR) with a collagen membrane from bovine pericardium and implantation of granular bovine bone biomaterial.

Muscle membrane dysfunction in critical illness myopathy assessed by velocity recovery cycles

To test the hypothesis that muscle fibers are depolarized in patients with critical illness myopathy by measuring velocity recovery cycles (VRCs) of muscle action potentials.

VEGF-A promotes intussusceptive angiogenesis in the developing chicken chorioallantoic membrane

To assess the impact of vascular endothelial growth factor (VEGF) on intussusceptive angiogenesis.

Statin therapy and the expression of genes that regulate calcium homeostasis and membrane repair in skeletal muscle

In skeletal muscle of patients with clinically diagnosed statin-associated myopathy, discrete signs of structural damage predominantly localize to the T-tubular region and are suggestive of a calcium leak. The impact of statins on skeletal muscle of non-myopathic patients is not known. We analyzed the expression of selected genes implicated in the molecular regulation of calcium and membrane repair, in lipid homeostasis, myocyte remodeling and mitochondrial function. Microscopic and gene expression analyses were performed using validated TaqMan custom arrays on skeletal muscle biopsies of 72 age-matched subjects who were receiving statin therapy (n = 38), who had discontinued therapy due to statin-associated myopathy (n = 14), and who had never undergone statin treatment (n = 20). In skeletal muscle, obtained from statin-treated, non-myopathic patients, statins caused extensive changes in the expression of genes of the calcium regulatory and the membrane repair machinery, whereas the expression of genes responsible for mitochondrial function or myocyte remodeling was unaffected. Discontinuation of treatment due to myopathic symptoms led to a normalization of gene expression levels, the genes encoding the ryanodine receptor 3, calpain 3, and dystrophin being the most notable exceptions. Hence, even in clinically asymptomatic (non-myopathic) patients, statin therapy leads to an upregulation in the expression of genes that are concerned with skeletal muscle regulation and membrane repair.

The contribution of surface residues to membrane binding and ligand transfer by the -tocopherol transfer protein ( -TTP)

Previous work has shown that the -tocopherol transfer protein ( -TTP) can bind to vesicular or immobilized phospholipid membranes. Revealing the molecular mechanisms by which -TTP associates with membranes is thought to be critical to understanding its function and role in the secretion of tocopherol from hepatocytes into the circulation. Calculations presented in the Orientations of Proteins in Membranes database have provided a testable model for the spatial arrangement of -TTP and other CRAL-TRIO family proteins with respect to the lipid bilayer. These calculations predicted that a hydrophobic surface mediates the interaction of -TTP with lipid membranes. To test the validity of these predictions, we used site-directed mutagenesis and examined the substituted mutants with regard to intermembrane ligand transfer, association with lipid layers and biological activity in cultured hepatocytes. Substitution of residues in helices A8 (F165A and F169A) and A10 (I202A, V206A and M209A) decreased the rate of intermembrane ligand transfer as well as protein adsorption to phospholipid bilayers. The largest impairment was observed upon mutation of residues that are predicted to be fully immersed in the lipid bilayer in both apo (open) and holo (closed) conformations such as Phe165 and Phe169. Mutation F169A, and especially F169D, significantly impaired -TTP-assisted secretion of -tocopherol outside cultured hepatocytes. Mutation of selected basic residues (R192H, K211A, and K217A) had little effect on transfer rates, indicating no significant involvement of nonspecific electrostatic interactions with membranes.

Periosteal Distraction Osteogenesis and Barrier Membrane Application: An Experimental Study in the Rat Calvaria

Background: Distraction of the periosteum results in the formation of new bone in the gap between the periosteum and the original bone. We postulate that the use of a barrier membrane would be beneficial for new bone formation in periosteal distraction. Methods: To selectively influence the contribution of the periosteum, a distraction plate with perforations was used alone or covered by a collagen barrier membrane. All animals were subjected to a 7-day latency period and a 10-day distraction period with a rate of 0.1 mm/day. Four animals per group with or without a barrier membrane were sacrificed at 2, 4, and 6 weeks after the end of the distraction. The height of new bone generated relative to the areas bound by the parent bone and the periosteum was determined by histomorphometric methods. Results: New bone was found in all groups. At the periphery of the distraction plate, significant differences in bone height were found between the hinge and the distraction screw for the group without barrier membrane at 2 weeks (0.39 ± 0.19 mm) compared to 4 weeks (0.84 ± 0.44 mm; P = 0.002) and 6 weeks (1.06 ± 0.39 mm; P = 0.004). Differences in maximum bone height with and without a barrier membrane were observed laterally to the distraction plate at 2 weeks (1.22 ± 0.64 versus 0.55 ± 0.14 mm; P = 0.019) and 6 weeks (1.61 ± 0.56 versus 0.73 ± 0.33 mm; P = 0.003) of the consolidation period. Conclusion: Within the limitations of the present study, the application of a barrier membrane may be considered beneficial for new bone formation induced by periosteal distraction.

Characteristics and dimensions of the Schneiderian membrane: a radiographic analysis using cone beam computed tomography in patients referred for dental implant surgery in the posterior maxilla

To determine the dimensions of the Schneiderian membrane using limited cone beam computed tomography (CBCT) in individuals referred for dental implant surgery, and to determine factors influencing the mucosal thickness.

Plasma membrane repair and cellular damage control: the annexin survival kit

Plasmalemmal injury is a frequent event in the life of a cell. Physical disruption of the plasma membrane is common in cells that operate under conditions of mechanical stress. The permeability barrier can also be breached by chemical means: pathogens gain access to host cells by secreting pore-forming toxins and phospholipases, and the host's own immune system employs pore-forming proteins to eliminate both pathogens and the pathogen-invaded cells. In all cases, the influx of extracellular Ca(2+) is being sensed and interpreted as an "immediate danger" signal. Various Ca(2+)-dependent mechanisms are employed to enable plasma membrane repair. Extensively damaged regions of the plasma membrane can be patched with internal membranes delivered to the cell surface by exocytosis. Nucleated cells are capable of resealing their injured plasmalemma by endocytosis of the permeabilized site. Likewise, the shedding of membrane microparticles is thought to be involved in the physical elimination of pores. Membrane blebbing is a further damage-control mechanism, which is triggered after initial attempts at plasmalemmal resealing have failed. The members of the annexin protein family are ubiquitously expressed and function as intracellular Ca(2+) sensors. Most cells contain multiple annexins, which interact with distinct plasma membrane regions promoting membrane segregation, membrane fusion and--in combination with their individual Ca(2+)-sensitivity--allow spatially confined, graded responses to membrane injury.

Detection of linear IgE deposits in bullous pemphigoid and mucous membrane pemphigoid: a useful clue for diagnosis

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease of the skin associated with IgG autoantibodies to BP180 and BP230, while mucous membrane pemphigoid (MMP) comprises a heterogeneous group of autoimmune blistering diseases characterized by a predominant mucous membrane involvement and scarring tendency associated with an autoantibody response to various autoantigens, including BP180. While the pathogenicity of IgG autoantibodies to BP180 has been demonstrated in BP, the role of IgE autoantibodies in mediating tissue damage in BP and MMP is unclear.