May-Thurner syndrome is a rare clinical entity involving venous obstruction of the left lower extremity. Obstruction occurs secondary to compression of the left common iliac vein between the right common iliac artery and the underlying vertebral body. Current management largely involves endovascular therapy. A review was conducted of six studies containing at least five patients with May-Thurner syndrome treated by endovascular therapy. We compiled data on 113 patients, analyzing patient demographics, treatment details, and outcome. An 18-year-old female presented 1 week after the onset of left lower extremity pain and swelling. Duplex ultrasonography revealed extensive left-sided deep venous thrombosis (DVT). Thrombolysis followed by iliac vein stent placement restored patency to the venous system, with subsequent resolution of symptoms. Review of 113 patients revealed that the majority were females (72%) presenting with DVT (77%), most of which was acute in onset (73%). Therapy consisted of catheter-directed thrombolysis and subsequent stent placement in the majority of patients, resulting in a mean technical success of 95% and a mean 1-year patency of 96%. Endovascular therapy is the current mainstay of treatment for May-Thurner syndrome. Review of the current literature supports treatment via catheter-directed thrombolysis followed by stent placement with good early results.

Adipose-derived stem cells (ASCs) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASCs isolated from elderly patients. Isolation of ASCs from 53 patients (50-89 years) revealed that advanced age or comorbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) than in younger. ASCs cultured in endothelial growth medium-2 for up to 3 weeks formed cords upon Matrigel and demonstrated acetylated-low-density lipoprotein and lectin uptake. Further stimulation with vascular endothelial growth factor and shear stress upregulated endothelial cell-specific markers (CD31, von Willebrand factor, endothelial nitric oxide synthase, and VE-cadherin). Inhibition of the PI 3 K but not mitogen-activated protein kinase pathway blocked the observed endothelial differentiation. Shear stress promoted an antithrombogenic phenotype as demonstrated by production of tissue-plasminogen activator and nitric oxide, and inhibition of plasminogen activator inhibitor-1. Shear stress augmented integrin a 5 b 1 expression and subsequently increased attachment of differentiated ASCs to basement membrane components. Finally, ASCs seeded onto a decellularized vein graft resisted detachment despite application of shear force up to 9 dynes. These results suggest that (1) advanced age and comorbidity do not negatively impact isolation of ASCs, and (2) these stem cells retain significant capacity to acquire key endothelial cell traits throughout life. As such, adipose tissue is a practical source of autologous stem cells for vascular tissue engineering. IntroductionU se of adult stem cells for vascular tissue engineering and regeneration continues to gain momentum as research reveals their improved potency and function. The majority of work involves mesenchymal stem cells (MSCs) derived from bone marrow aspiration and endothelial progenitor cells (EPCs) obtained from blood. Each of these cell types have been used to line vascular scaffolds in the creation of a tissue engineered bypass graft [1][2][3], as well as in various strategies to promote therapeutic angiogenesis in the coronary and peripheral circulations [4][5][6][7]. Although these cells are appropriate for vascular tissue engineering, their availability in patients most likely to benefit from this technology raises practical concerns. The number of stem and progenitor cells derived from bone marrow and blood decrease significantly with age and patient comorbidity [8][9][10]. Further, it has also been suggested that differentiation potential of bone-marrow-derived MSCs decreases with age [11]. Recent data also indicate that EPC function is diminished in patients with severe vascular disease and multiple coronary risk factors [12,13].An alternative source for autologous adult stem cells is adipose tissue. Adipose-derived stem cells (ASCs) are multipotent, with the capacity to differentiate into adipocytes, chondrocytes,...

Listeria monocytogenes grows in the cytosol of mammalian cells and spreads from cell to cell without exiting the intracellular milieu. During cell–cell spread, bacteria become transiently entrapped in double‐membrane vacuoles. Escape from these vacuoles is mediated in part by a bacterial phospholipase C (PC‐PLC), whose activation requires cleavage of an N‐terminal peptide. PC‐PLC activation occurs in the acidified vacuolar environment. In this study, the pH‐dependent mechanism of PC‐PLC activation was investigated by manipulating the intracellular pH of the host. PC‐PLC secreted into infected cells was immunoprecipitated, and both forms of the protein were identified by SDS–PAGE fluorography. PC‐PLC activation occurred at pH 7.0 and lower, but not at pH 7.3. Total amounts of PC‐PLC secreted into infected cells increased several‐fold over controls within 5 min of a decrease in intracellular pH, and the active form of PC‐PLC was the most abundant species detected. Bacterial release of active PC‐PLC was dependent on Mpl, a bacterial metalloprotease that processes the proform (proPC‐PLC), and did not require de novo protein synthesis. The amount of proPC‐PLC released in response to a decrease in pH was the same in wild‐type and Mpl‐minus‐infected cells. Immunofluorescence detection of PC‐PLC in infected cells was performed. When fixed and permeabilized infected cells were treated with a bacterial cell wall hydrolase, over 97% of wild‐type and Mpl‐minus bacteria stained positively for PC‐PLC, in contrast to less than 5% in untreated cells. These results indicate that intracellular bacteria carry pools of proPC‐PLC. Upon cell–cell spread, a decrease in vacuolar pH triggers Mpl activation of proPC‐PLC, resulting in bacterial release of active PC‐PLC.

Membrane immunoglobulin M (mIgM) and mIgD are major B-lymphocyte antigen receptors, which function by internalizing antigens for processing and presentation to T cells and by transducing essential signals for proliferation and differentiation. Although ligation of mIgM or mIgD results in rapid activation of a phospholipase C and a tyrosine kinase(s), these receptors have cytoplasmic tails of only three amino acid residues (Lys-Val-Lys), which seem ill suited for direct physical coupling with cytoplasmic signal transduction structures. In this report, we identify the a, 13, and Y components of the mIgM-associated phosphoprotein complex, which may play a role in signal transduction. Proteolytic peptide mapping demonstrated that the IgM-a chain differs from Ig-13 and Ig-y. The chains were purified, and amino-terminal sequencing revealed identity with two previously cloned B-cellspecific genes. One component, IgM-a, is a product of the mb-i gene, and the two additional components, Ig-J3 and Ig-y, are products of the B29 gene. Immunoblotting analysis using rabbit antibodies prepared against predicted peptide sequences of each gene product confirmed the identification of these mIgMassociated proteins. The deduced sequence indicates that these receptor subunits lack inherent protein kinase domains but include common tyrosine-containing sequence motifs, which are likely sites of induced tyrosine phosphorylation.Membrane-bound immunoglobulin M (mIgM) and mIgD are major B-lymphocyte surface structures that specifically bind antigen and subsequently transduce growth-modulating signals. Ligation of either mIgM or mIgD with polyvalent antigen or anti-immunoglobulin antibodies results in the rapid activation of a polyphosphoinositide-specific phospholipase C, which generates calcium-mobilizing inositol polyphosphates and protein kinase C-activating diacylglycerol (1, 2). Recent evidence from several laboratories has established that a tyrosine kinase is also activated upon B-cell antigen receptor ligation (3,4) and that ligand-induced phospholipase C activation is kinase dependent (5). Candidates for the tyrosine kinase include Lyn, which has been shown to associate with mIgM (6), and Blk, which is B-cell-specific (7). Interestingly, mIgM and mIgD have minimal cytoplasmic structure [a Lys-Val-Lys (KVK) sequence] on each of two membrane-spanning heavy chains (8-10), which is probably incapable of direct physical coupling to such cytoplasmic signaling structures.Recently B-cell antigen receptor-associated structures have been identified that may play an important role in physical coupling to signal transduction structures, analogous to CD3 components in association with the T-cell antigen receptor. Multiple components of the mIgMassociated glycoprotein complex have been defined biochemically by several laboratories (11-16) and designated IgM-a (32 kDa), Ig-,B (37 kDa), and Ig-y(34 kDa) (13,14). All ofthese components are inducibly phosphorylated on tyrosine residues upon receptor ligation or treatment of cells with alum...

No abstract

No abstract

No abstract

No abstract