The use of surface immobilization of P-selectin glycoprotein ligand-1 on mesenchymal stem cells to facilitate selectin mediated cell tethering and rolling

Mesenchymal stem/stromal cells (MSCs) are an important candidate for cell-based therapy since they can be easily isolated and expanded, secrete beneficial paracrine factors, and differentiate into multiple lineages. Since the endothelium at sites of injury and inflammation often express adhesion molecules belonging to the selectin family, methods to endow MSCs with selectin-ligands can enhance the efficacy of cell delivery and tissue engraftment. Here, we describe a construct 19Fc[FUT7⁺], where the first 19 amino acids of the pan-selectin ligand PSGL-1 (P-selectin glycoprotein ligand-1) was fused to a human IgG1. When expressed in HEK293T cells over-expressing the α(1,3)fucosyltransferase FUT7, 19Fc[FUT7⁺] is decorated by a core-2 sialyl Lewis-X sialofucosylated O-glycan. The non-covalent coupling of this protein onto MSC surface using palmitated protein G (PPG) enhanced cell binding to E- and P-selectin under hydrodynamic shear, without altering MSC multipotency. MSCs functionalized with 19Fc[FUT7⁺] were captured/tethered onto stimulated endothelial cell monolayers at wall shear stresses up to 4 dyn/cm². Once captured, the cells rolled robustly up to the highest shear stress tested, 10 dyn/cm². Unlike previous work where MSCs could only be captured onto selectin-bearing substrates at low or no-flow conditions, the current work presents a ‘glycan engineering’ strategy to enable leukocyte-like capture and rolling.     

Wound healing grafts: Omega‐3 fatty acid lipid content differentiates the lipid profiles of acellular Atlantic cod skin from traditional dermal substitutes

Acellular fish skin (ACS) has emerged as a dermal substitute used to promote wound healing with decreased scar formation and pain relief that may be due to polyunsaturated fatty acid (PUFA) content. However, the PUFA content of ACS is still unknown. The aim of this study was to compare the total fatty acids and lipid profiles of ACS to two bovine‐based grafts and standard of care human cadaver skin (HCS). Furthermore, there was also the goal to assess the capability of ACS lipid content to enhance wound healing. The fatty acid analysis was performed with GC–FID, and an LC–MS untargeted method was developed in order to the analyse the lipid profiles of the grafts was. The enhancement of wound healing by the ACS extract was investigated in vitro on HaCat cells. Our results showed that ACS had the highest content of PUFA (27.0 ± 1.43% of their total fatty acids), followed by HCS (20.6 ± 3.9%). The two grafts of bovine origin presented insignificant PUFA amounts. The majority of the PUFAs found in ACS were omega‐3, and in HCS, they were omega‐6. The untargeted lipidomics analysis demonstrated that ACS grafts were characterized by phosphatidylcholine containing either 20:5 or 22:6 omega‐3 PUFA. The ACS lipid extract increased the HaCat cells migration and enhanced wound closure 4 hr earlier versus control. Our study demonstrated that ACS has a lipid profile that is distinct from other wound healing grafts, that PUFAs are maintained in ACS post‐processing as phosphatidylcholine, and that ACS lipid content influences wound healing properties.     

Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus

Antibodies to double-stranded DNA (dsDNA) are prevalent in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis, yet the nature and regulation of antigenic cell-free DNA (cfDNA) are poorly understood. Null mutations in the secreted DNase DNASE1L3 cause human monogenic SLE with anti-dsDNA autoreactivity. We report that >50% of sporadic SLE patients with nephritis manifested reduced DNASE1L3 activity in circulation, which was associated with neutralizing autoantibodies to DNASE1L3. These patients had normal total plasma cfDNA levels but showed accumulation of cfDNA in circulating microparticles. Microparticle-associated cfDNA contained a higher fraction of longer polynucleosomal cfDNA fragments, which bound autoantibodies with higher affinity than mononucleosomal fragments. Autoantibodies to DNASE1L3-sensitive antigens on microparticles were prevalent in SLE nephritis patients and correlated with the accumulation of cfDNA in microparticles and with disease severity. DNASE1L3-sensitive antigens included DNA-associated proteins such as HMGB1. Our results reveal autoantibody-mediated impairment of DNASE1L3 activity as a common nongenetic mechanism facilitating anti-dsDNA autoreactivity in patients with severe sporadic SLE.     

Transfemoral use of the guideLiner catheter in complex coronary and bypass graft interventions

The GuideLiner catheter (Vascular Solutions, Minneapolis, MN) is a novel, rapid exchange catheter that allows deep vessel intubation. We describe 21 patients in whom the GuideLiner catheter [7 French (F) in 76% and 6F in 24%] was used to facilitate equipment delivery (n = 14) or vessel engagement (n = 7). Pressure dampening after GuideLiner catheter insertion was observed in 12 patients (57%). The procedure was successfully completed in 19 patients (90%) and one patient developed acute vessel closure, likely due to dissection. The GuideLiner catheter can facilitate complex coronary interventions but should be used with caution to minimize the risk for vessel injury. © 2011 Wiley Periodicals, Inc.     

Patients' profiles and perceptions of complete dentures in a university dental clinic

This study investigated factors associated with perceptions of complete dentures (CDs) among patients presenting at a university dental clinic. A retrospective chart review of all new edentulous patients presenting at the Athens University School of Dentistry Removable Prosthodontics Clinic between 1993 and 2002 (n = 2,526) was completed. More than half of CD-wearing patients were dissatisfied with their dentures at the initial visit. Dissatisfaction was correlated with current use of denture adhesives and less time spent edentulous and was more prevalent among females. Factors affecting patients? adaptation to and satisfaction with CDs should be considered at CD fabrication and follow-up.     

Successful Management of a Postinfarction Left Ventricular Rupture Using a Sutureless Technique With Concomitant Myocardial Revascularization

A bstract We present a case of left ventricular (LV) rupture that occurred on the second day after inferolateral myocardial infarction (MI). An aggressive diagnostic approach with rapid coronary angiography prior to surgical repair provides a benefit characterized postoperatively by complete recovery of myocardial contractility in the akinetic infarcted area. We believe that coronary artery disease associated with subacute ventricular rupture may, in fact, be better investigated and simultaneously treated under a protocol of early surgical repair.     

Late isolated brain metastasis following enucleation for choroidal melanoma.

Brain metastases from choroidal melanoma are rare and usually have a grave prognosis. A case of successfully treated late isolated brain metastasis from choroidal melanoma is described. A 35-year-old man presented with epileptic seizures of recent origin, 9 years following enucleation for choroidal melanoma. Imaging studies revealed a lesion of the right frontal lobe that was surgically removed. Results of pathologic examination were compatible with metastatic choroidal melanoma. The patient is asymptomatic 5 years postoperatively. Late isolated brain metastases from uveal melanoma may be treatable by local resection. Close, lifelong follow-up is required to diagnose and aggressively treat metastatic disease.