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Notes: Background: Intravascular ultrasound (IVUS) is the reference method for in vivo assessment of vessel dimensions and coronary plaque composition, which can influence device selection as well as stent sizing. Objectives: The objective of this prospective multicenter-study was to test the application, safety, and feasibility of a new combined IVUS and stent delivery system. Methods: A total of 32 patients with planned direct stent implantation under IVUS guidance were included in the study. Procedural as well as angiographical and IVUS characteristics of the stent implantation with the combined IVUS and stent delivery system were assessed and compared to a historical control cohort where IVUS-guided stenting was performed with a separate IVUS catheter. Results: Direct stent placement was successfully performed in all patients and no malfunctions of the system were noted. A postinterventional IVUS assessment was possible in 27 (87%) of the 31 patients. The IVUS information led to a change in therapeutic strategy in 16 (50%) of the 32 patients. In the study group, both the procedural time and the amount of contrast dye were significantly lower than in the historical IVUS-guided stenting control group. A clinical 12-month follow-up revealed a 89% event-free survival and a target vessel revascularization rate of 7%. Conclusion: The use of a combined IVUS and stent delivery device is safe, easy to handle, and can provide helpful additional information to guide a percutaneous coronary interventions procedure. Beyond angiography, these informations had significant impact on the interventional strategy in these patients, which resulted in a low rate of major adverse cardiac events. The concept of combining IVUS information and a stent delivery system may be increasingly attractive with evolving imaging modalities like virtual histology or a combination with drug-eluting stents.

Notes: Organic–inorganic ultraviolet (UV) active hybrid materials have been prepared by a sol-gel process from benzophenone derivatives and tetraethylorthosilicate. The silica particles are spherical in shape and have a narrow size distribution which remains unchanged up to organic chromophore concentrations of 0.2 mmol g−1. At higher concentrations the spheres become less regular and fuse. A dependence of the material absorption properties on the particle size (at the same organic chromophore concentration) and on the concentration of surface grafted chromophores was noted. The most effective UV filter materials were found in a combination of silica incorporated chromophores and surface grafted chromophores at an overall low chromophore concentration. A comparison of the photostability of chromophores at standardized UV irradiation revealed an increase in stability for silica incorporated and surface immobilized benzophenone compared to benzophenone in a homogeneous solution.

Notes: Scleredema adultorum is a rare connective tissue disorder of unknown cause. Both bath-PUVA and cream-PUVA therapy were reported to be effective. We describe a patient with scleredema adultorum who showed a striking clinical improvement with a medium-dose UVA1 phototherapy (single dose, 50 J/cm2; 35 treatments).

Notes: Digital cushions were studied in horses with particular reference to vascularization, tissue constituents and matrix components. The cushions mainly resembled a network of coarse collagen bundles. The areas inbetween the bundles were replenished with loosely woven interstitial connective tissue, myxoid tissue, and fibrocartilage. Expected masses of fat lobules were missing: only solitary adipocytes or small groups of adipocytes were seen. Vascular supply to the cushions was remarkably poor. The mucinous myxoid matrix largely consisted of hyaluronan with little sulphated glycosaminoglycans. Myxoid cells were stellate or ramified in shape and showed a tendency to store glycogen and lipid droplets. Myxoid cells reacted for vimentin and stained for S-100 protein. Moreover, myxoid cells often reacted for neuron specific enolase and glial fibrillary acidic protein. Myxoid tissue continuously transformed into loosely organized interstitial connective tissue with fibroblasts, which remained unreactive when tested for neuroectodermal markers. Myxoid tissue also was not clearly demarcated against irregularly interspersed islets of fibrocartilage or hyaline cartilage. Chondrocytes did not stain for neuron specific enolase but reactivity for S-100 protein and glial fibrillary acidic protein was noted in peripheral regions of fibrocartilage. Single or grouped unilocular fat cells were rarely placed into myxoid areas. Unilocular fat cells stained for vimentin, S-100 protein, and occasionally for glial fibrillary acidic protein but not for neuron specific enolase. Continuous transformation of myxoid tissue into cartilage together with corresponding reactivity for neuroectodermal marker proteins of myxoid cells and peripherally located chondrocytes suggest close relationship between myxoid cells and chondrocytes. The same criteria indicate relationship between myxoid cells and adipocytes. Coarse connective tissue, myxoid tissue, fibrous cartilage, and fat cells are functionally combined to absorb mechanical shock in the horse digital cushions.

Notes: Hypoglycaemia induced by insulin injection is a powerful stimulus to the hypothalamic-pituitary-adrenal (HPA) axis and drives the secretion of corticotropin-releasing hormone and vasopressin from the neurones in the paraventricular nucleus (PVN), as well as the downstream hormones, adrenocorticotropic hormone and corticosterone. In some brain regions, hypoglycaemia also provokes increases in extracellular fluid concentrations of glutamate. Regulation of glutamatergic mechanisms could be involved in the control of the HPA axis during hypoglycaemic stress and one potential site of regulation might be at the receptors for glutamate, which are expressed in the PVN. Insulin (2.0 IU/kg, i.p.) or saline was administered to adult male Sprague-Dawley rats and the animals were sacrificed 30 min, 180 min and 24 h after injection. The amount of several kainic acid-preferring glutamate receptor mRNAs (i.e. KA2, GluR5 and GluR6) were assessed in the PVN by in situ hybridisation histochemistry. Injection of insulin induced a rapid fall in plasma glucose concentrations, which was mirrored by an increase in plasma corticosterone concentrations. KA2 and GluR5 mRNAs are highly expressed within the rat PVN, and responded to hypoglycaemia with robust increases in expression that endured beyond the period of hypoglycaemia itself. However, GluR6 mRNA is expressed in the areas adjacent to the PVN and hypoglycaemic stress failed to alter expression of this mRNA. These experiments suggest that kainic acid-preferring glutamate receptors are responsive to changes in plasma glucose concentrations and may participate in the activation of the PVN neurones during hypoglycaemic stress.

Notes: Background Toll-like receptor 9 (TLR9) is a pattern-recognition receptor that detects unmethylated CpG motifs prevalent in bacterial and viral DNA. TLR9 stimulation is a key event after bacterial infection, triggering innate immunity and T-helper type 1 skewed adaptive immunity. Synthetic CpG-oligodeoxynucleotides (CpG-ODNs) represent a promising and novel class of immune adjuvants for allergy treatment, vaccination, and cancer therapy. However, common functional TLR9 gene variants could interfere with the clinical utilization of CpG-ODN in immunotherapy. Recently, a possible association of TLR9 polymorphism C-1237T with asthma has been reported.Objective The aim of the present study was to investigate whether TLR9 polymorphisms or haplotypes have functional relevance and are associated with atopy.Methods We genotyped five common TLR9 single-nucleotide polymorphisms (SNPs) in promoter, exon, and intron regions of the gene in 527 healthy blood donors, and estimated four common haplotypes. The total IgE and specific IgE levels against the most common aeroallergens were measured (n=303). IFN-α production by plasmacytoid dendritic cells (pDCs) was analysed after stimulation with TLR9 ligand CpG-ODN (n=220).Results No significant influence of common TLR9 polymorphisms and haplotypes on the total and specific IgE levels was found. Functional analysis of CpG-ODN-induced IFN-α did not indicate a significant role for common TLR9 gene polymorphisms in TLR9 function.Conclusion We conclude that common genetic differences in the TLR9 gene exert no major influence on allergy susceptibility, and are unlikely to have on impact on clinical application of CpG-ODNs.

Notes: The availability of neuropeptides or neuroendocrine hormones as important modulators of innate and adaptive immune responses is effectively controlled by neuropeptide-specific peptidases. In previous studies, drug inhibition or genomic deletion of neutral endopeptidase (NEP, CD10) or of angiotensin-converting enzyme (ACE, CD143) resulted in a profound augmentation of murine allergic contact dermatitis responses. Likewise, we have identified dermal microvascular endothelial cells (EC) as both source and target of the proopiomelanocortin (POMC) peptides ACTH and α-melanocyte-stimulating hormone (α-MSH), in particular. EC express melanocortin receptor (MC-) 1 and α-MSH is capable of profoundly downregulating LPS- or cytokine-induced expression of adhesion molecules in vitro and of endotoxin-induced cutaneous vasculitis in vivo. In this study, we have tested the hypothesis that NEP or ACE expressed by EC may influence the local bioavailability of POMC peptides. Cell membranes prepared from the high NEP/low ACE expressing human microvascular endothelial cell line 1 (HMEC-1) or from low NEP/high ACE expressing primary human dermal EC (HDMEC) were incubated for 30–480 min with ACTH1–39 in the presence or absence of NEP or ACE inhibitors, respectively. Analysis of membrane supernatants for ACTH and α-MSH by radioimmunoassay revealed a decrease in ACTH immunoreactivity (IR) over time that could be partially blocked with NEP inhibitors. In parallel, α-MSH IR increased peaking after 60 min. Fragments generated by incubation of HMEC-1 or HDMEC membranes with ACTH1–39, ACHT1–24 or α-MSH for 1–120 min were further analyzed by Matrix-assisted-LASER desorption time-of-flight (MALDI-TOF) spectroscopy. HMEC-1 membranes generated main peptide products with molecular masses of 2007, 1057 and 945, respectively, from ACTH1–39, and 1057 from ACTH1–24. Inhibition with NEP, but not ACE inhibitors altered the fragmentation profile indicating that NEP is involved in degradation of both ACTH1–39 and ACTH1–24. Likewise, HDMEC membranes fragmented ACTH similar to HMEC-1 membranes in the presence of NEP inhibitors. Both HMEC-1 and HDMEC membranes were also capable of slowly degrading α-MSH suggesting that EC proteolytic peptidases are important for the local control of ACTH/α-MSH bioavailability, which may play a significant role in controlling local cutaneous inflammatory responses.

Notes: We provide a functional and regulatory analysis of glcP, encoding the major glucose transporter of Streptomyces coelicolor A3(2). GlcP, a member of the Major Facilitator Superfamily (MFS) of bacterial and eucaryotic sugar permeases, was found to be encoded twice at two distinct loci, glcP1 and glcP2, located in the central core and in the variable right arm of the chromosome respectively. Heterologous expression of GlcP in Escherichia coli led to the full restoration of glucose fermentation to mutants lacking glucose transport activity. Biochemical analysis revealed an affinity constant in the low-micromolar range and substrate specificity for glucose and 2-deoxyglucose. Deletion of glcP1 but not glcP2 led to a drastic reduction in growth on glucose reflected by the loss of glucose uptake. This correlated with transcriptional analyses, which showed that glcP1 transcription was strongly inducible by glucose, while glcP2 transcripts were barely detectable. In conclusion, GlcP, which is the first glucose permease from high G+C Gram-positive bacteria characterized at the molecular level, represents the major glucose uptake system in S. coelicolor A3(2) that is indispensable for the high growth rate on glucose. It is anticipated that the activity of GlcP is linked to other glucose-mediated phenomena such as carbon catabolite repression, morphogenesis and antibiotic production.

Notes: [Auszug] DNA methylation is the most stable type of epigenetic modification modulating the transcriptional plasticity of mammalian genomes. Using bisulfite DNA sequencing, we report high-resolution methylation profiles of human chromosomes 6, 20 and 22, providing a resource of about 1.9 million CpG ...