Prevalence of valvular heart disease in cardiac amyloidosis and impact on survival.

Background: Limited data exists on the prognostic impact of valvular heart disease in cardiac amyloidosis (CA). We therefore sought to define the prevalence of valvular disease in patients with CA and assess the effects of significant valve disease on survival.

Methods: This multi-center retrospective cohort study included consecutive patients with confirmed transthyretin (TTR) or light chain (AL) amyloidosis.

Myosin light chain 6 (Myl6) interacts with kindlin-3 and is required to support integrin αβ activation in platelets in mice.

Background: Kindlin-3 in platelets plays an essential role in supporting integrin αβ activation, platelet spreading, aggregation, and clot retraction by binding to the integrin β cytoplasmic tail. However, the mechanism by which kindlin-3 mediates the crosstalk between integrin αβ and myosin in platelets remains unknown.

Objectives: To examine the role of myosin light chain 6 (Myl6) in supporting integrin αβ activation in platelets.

Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice.

Objective And Design: An accumulating body of evidence has shown that gut microbiota is involved in regulating inflammation; however, it remains undetermined if and how gut microbiota plays an important role in modulating deep venous thrombosis (DVT), which is an inflammation-involved thrombotic event.

Subjects: Mice under different treatments were used in this study.

Methods And Treatment: We induced stenosis DVT in mice by partially ligating the inferior vena cava.

Kindlin-3 in Immune Cells Is Required to Suppress Prostate Cancer Tumor Growth in Mice.

Background/aim: Kindlins are essential integrin activators. Kindlin-1 and kindlin-2 are often concomitantly expressed in epithelial tumor cells and participate in regulating tumor malignancy. However, it remains unclear whether kindlin-3, the one expressed in immune cells, also plays a role in regulating tumor malignancy.

Paxillin binding to the PH domain of kindlin-3 in platelets is required to support integrin αIIbβ3 outside-in signaling.

Background: Kindlin-3 is essential for supporting the bidirectional signaling of integrin αIIbβ3 in platelets by bridging the crosstalk between integrin αIIbβ3 and the cytoplasmic signaling adaptors.

Objective: In this study, we identified a previously unrecognized paxillin binding site in the pleckstrin homology (PH) domain of kindlin-3 and verified its functional significance.

Methods: Structure-based approaches were employed to identify the paxillin binding site in the PH domain of kindlin-3.

β3-Endonexin interacts with ninein in vascular endothelial cells to promote angiogenesis.

Anti-angiogenesis serves as an effective tumor therapy approach. In a previous study, we found that β3-endonexin expressed in vascular endothelial cells was involved in promoting proliferation and angiogenesis partially by facilitating VEGF expression. However, it still remains unclear if β3-endonexin in vascular endothelial cells also employs other mechanisms in regulating angiogenesis.

Structure basis of the FERM domain of kindlin-3 in supporting integrin αIIbβ3 activation in platelets.

Kindlin-3, a protein 4.1, ezrin, radixin, and moesin (FERM) domain-containing adaptor in hematopoietic cells, is essentially required for supporting the bidirectional integrin αIIbβ3 signaling in platelets by binding to the integrin β3 cytoplasmic tail. However, the structural details of kindlin-3's FERM domain remain unknown.

Kindlin-3 in platelets and myeloid cells differentially regulates deep vein thrombosis in mice.

Platelets and myeloid cells cooperate to promote deep vein thrombosis (DVT). Here we evaluated the role of kindlin-3, a key integrin activator in these cells, in regulating stenosis-induced DVT in mice. DVT was significantly suppressed in mice that express a kindlin-3 mutant defective for integrin binding, showing that kindlin-3-mediated integrin signaling in blood cells is required for DVT.

Sharpin suppresses β1-integrin activation by complexing with the β1 tail and kindlin-1.

Background: Previously sharpin has been identified as an endogenous inhibitor of β1-integrin activation by directly binding to a conserved region in the cytoplasmic tails (CTs) of the integrin β1-associated α subunits.

Methods: Here we employed biochemical approaches and cellular analyses to evaluate the function and molecular mechanism of the sharpin-kindlin-1 complex in regulating β1-integrin activation.

Results: In this study, we found that although the inhibition of sharpin on β1-integrin activation could be confirmed, sharpin had no apparent effect on integrin αIIbβ3 activation in CHO cell system.

Kindlin supports platelet integrin αIIbβ3 activation by interacting with paxillin.

Kindlins play an important role in supporting integrin activation by cooperating with talin; however, the mechanistic details remain unclear. Here, we show that kindlins interacted directly with paxillin and that this interaction could support integrin αIIbβ3 activation. An exposed loop in the N-terminal F subdomain of kindlins was involved in mediating the interaction.

Interaction of kindlin-3 and β2-integrins differentially regulates neutrophil recruitment and NET release in mice.

Kindlin-3 essentially supports integrin activation in blood cells. Absence of kindlin-3 in humans causes leukocyte adhesion deficiency-III characterized with severe bleeding disorder and recurrent infections. Previously, we generated kindlin-3 knock-in (K3KI) mice carrying an integrin-interaction disrupting mutation in kindlin-3 and verified the functional significance of the binding of kindlin-3 to integrin αIIbβ3 in platelets.

Dickkopf homologs in squamous mucosa of esophagitis patients are overexpressed compared with Barrett's patients and healthy controls.

Objectives: Esophageal mucosal response to acid exposure varies from minimal changes to erosions/ulcerations and Barrett's metaplasia. While differences in acid contact time have been suggested, the reason for these different responses is not completely understood. The aim of this study was to identify and compare gene expression differences between normal distal and proximal squamous esophageal mucosa (SM) in esophagitis patients with that of healthy controls and Barrett's patients.

Dose perturbations due to contrast medium and air in MammoSite treatment: An experimental and Monte Carlo study.

In the management of early breast cancer, a partial breast irradiation technique called MammoSite (Proxima Therapeutic Inc., Alpharetta, GA) has been advocated in recent years. In MammoSite, a balloon implanted at the surgical cavity during tumor excision is filled with a radio-opaque solution, and radiation is delivered via a high dose rate brachytherapy source situated at the center of the balloon.

Kinetics of urea exchange in air-filled and fluid-filled rat lungs.

Urea has been used as an indicator for estimating 1) the dilution of epithelial lining fluid (ELF) that occurs during bronchoalveolar lavage (BAL) and 2) the permeability-surface area product (PS) of the pulmonary endothelium to this solute. Because relatively little is known about how urea equilibrates with fluid in the lung tissues and airspaces, we have undertaken a study of the kinetics of movement from the vasculature into the tissues of isolated, perfused rat lungs. Although instillation of 5 ml of 154 mM saline into the airspaces of this preparation increased the calculated extravascular volume of 3HOH from 0.

MR imaging of the lateral collateral ligament of the ankle.

The ankle is stabilized by three sets of ligaments: the medial collateral (deltoid) ligament, the syndesmotic ligamentous complex, and the lateral collateral ligament. Of these three, the lateral collateral ligament is the one most often injured in ankle sprains. Assessment of the extent of injury has classically relied on clinical evaluation; plain film radiographs (including stress views); and, in some acute situations, ankle arthrography and/or peroneal tenography.