P-glycoprotein promotes epithelial T helper 2-associated cytokine secretion in chronic sinusitis with nasal polyps.

Background: Sinonasal epithelial cells are recognized as drivers of inflammation in chronic sinusitis with nasal polyps (CRSwNP) through secretion of T helper 2 (Th2)-promoting cytokines. P-glycoprotein (P-gp) is overexpressed in nasal polyps and modulates epithelial cytokine secretion in healthy mucosa. The objective of this study is to determine whether P-gp overactivity promotes Th2-associated cytokine secretion in CRSwNP.

[Effectiveness of pre-operative education in reducing anxiety in surgical patients].

Objective: To evaluate the effectiveness of a structured pre-operative interview conducted by operating room nurses in order to reduce the pre-operative anxiety of patients, and to determine the profile of patients who can benefit from it.

Material And Methods: A randomised double-blind and prospective trial was conducted on a sample of 335 patients scheduled for surgery in two regional hospitals in the Basque Region of Spain, Alto Deba Hospital and Mendaro Hospital. We compared the alternative of using a structured briefing (test group) with the current situation without any formal intervention (control group).

Interaction of intracorporeal lithotripters with Proteus mirabilis inoculated inside artificial calcium and struvite stones.

Background And Purpose: Renal calculi may contain bacteria that can remain active inside the stone and produce bacteremia and/or endotoxemia after lithotripsy. Urinary tract infection associated with urinary stones represents high morbidity. The purpose of this research was to use novel artificial struvite stones inoculated with living bacteria and to study the effect of four different intracorporeal lithotripters on bacterial inactivation after in vitro lithotripsy.

Interaction of shockwaves with infected kidney stones: is there a bactericidal effect?

Background And Purpose: Many calculi contain bacteria, which can remain active inside kidney stones and cause infection after lithotripsy. Reduction in renal infections after extracorporeal shockwave lithotripsy has been observed; however, results are controversial, and no information on the effect of shockwaves on bacteria inside kidney stones has been reported. The purpose of this research was to study whether bacteria inside kidney stones can be inactivated by shockwaves.

Inactivation of bacteria inoculated inside urinary stone-phantoms using intracorporeal lithotripters.

Intracorporeal lithotripsy is used to treat a high percentage of urinary calculi. Urinary calculi may contain bacteria, which might cause septicemia after lithotripsy; however, little is known about the effects of lithotripters on the viability of microorganisms inside renal calculi. The objectives of this study were to evaluate the bactericidal effect, and the potential effect on intra-bacterial protein release of four different intracorporeal lithotripters on Escherichia coli (E.

Primary synovial sarcoma of the lung.

A 45 -year-old woman presented chest pain and a well-defined oval shaped mass on a chest radiograph. A malignant pulmonary tumor was suspected and a right pneumonectomy was performed. The tumor measured about 13 x 12 cm, was pale-yellow in color and soft in texture.

Activin A stimulates IkappaB-alpha/NFkappaB and RANK expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors.

Recent studies have reported that activin A enhances osteoclastogenesis in cultures of mouse bone marrow cells stimulated with receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). However, the exact mechanisms by which activin A functions during osteoclastogenesis are not clear. RANKL stimulation of RANK/TRAF6 signaling increases nuclear factor-kappaB (NFkappaB) nuclear translocation and activates the Akt/PKB cell survival pathway.

Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression.

Osteopontin (OPN) was expressed in murine wild-type osteoclasts, localized to the basolateral, clear zone, and ruffled border membranes, and deposited in the resorption pits during bone resorption. The lack of OPN secretion into the resorption bay of avian osteoclasts may be a component of their functional resorption deficiency in vitro. Osteoclasts deficient in OPN were hypomotile and exhibited decreased capacity for bone resorption in vitro.

PTEN regulates RANKL- and osteopontin-stimulated signal transduction during osteoclast differentiation and cell motility.

PTEN (also known as MMAC-1 or TEP-1) is a frequently mutated tumor suppressor gene in human cancer. PTEN functions have been identified in the regulation of cell survival, growth, adhesion, migration, and invasiveness. Here, we characterize the diverse signaling networks modulated by PTEN in osteoclast precursors stimulated by RANKL and osteopontin (OPN).

Phosphatidylinositol 3,4,5-trisphosphate directs association of Src homology 2-containing signaling proteins with gelsolin.

Podosomes are adhesion structures in osteoclasts and are structurally related to focal adhesions mediating cell motility during bone resorption. Here we show that gelsolin coprecipitates some of the focal adhesion-associated proteins such as c-Src, phosphoinositide 3-kinase (PI3K), p130(Cas), focal adhesion kinase, integrin alpha(v)beta(3), vinculin, talin, and paxillin. These proteins were inducibly tyrosine-phosphorylated in response to integrin activation by osteopontin.

Receptor-operated osteoclast calcium sensing.

Osteoclasts "sense" elevated extracellular calcium, which leads to cytoskeletal changes that may be linked to phospholipase C (PLC) activation and the associated rise in intracellular calcium ([Ca(2+)](i)). Since PLC is linked to transient receptor potential channels (trp), we hypothesized that receptor activated calcium influx due to this channel type would be activated by osteoclasts sensing [Ca(2+)](e). We found that high [Ca(2+)](e) induced similar intracellular Ca(2+) rises in chicken osteoclasts with or without intracellular Ca(2+) store depletion by either TPEN or thapsigargin, thus defining store-insensitive Ca(2+) influx.

Rac is essential in the transformation of endothelial cells by polyoma middle T.

Expression of the Polyoma Middle T (PyMT) antigen in endothelial cells results in single-step transformation to hemangioma producing malignant cells. To study the mechanism of PyMT transformation, we used the PyMT induced mouse brain endothelial cell line, bEND.3, expressing constitutively active and dominant negative mutants of the small GTPase Rac.

Rho-A is critical for osteoclast podosome organization, motility, and bone resorption.

Rho plays a regulatory role in the formation of actin stress fibers and focal adhesions, and it is also involved in integrin-mediated signaling events. To study the role of Rho in alpha(v)beta(3)/gelsolin-dependent signaling, the HIV-Tat peptide, hemagglutinin (HA)-tagged Rho(Val-14) (constitutively active) and Rho(Asn-19) (dominant negative) were transduced into avian osteoclasts. Protein transduction by HA-Tat was highly efficient, and 90-100% of the cells were transduced with HA-tagged proteins.

Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength.

Osteoclasts are unique cells that utilize podosomes instead of focal adhesions for matrix attachment and cytoskeletal remodeling during motility. We have shown that osteopontin (OP) binding to the alpha(v)beta(3) integrin of osteoclast podosomes stimulated cytoskeletal reorganization and bone resorption by activating a heteromultimeric signaling complex that includes gelsolin, pp(60c-src), and phosphatidylinositol 3'-kinase. Here we demonstrate that gelsolin deficiency blocks podosome assembly and alpha(v)beta(3)-stimulated signaling related to motility in gelsolin-null mice.

Volume regulatory decrease in UMR-106.01 cells is mediated by specific alpha1 subunits of L-type calcium channels.

An early cellular response of osteoblasts to swelling is plasma membrane depolarization, accompanied by a transient increase in intracellular calcium ([Ca2+]i), which initiates regulatory volume decrease (RVD). The authors have previously demonstrated a hypotonically induced depolarization of the osteoblast plasma membrane, sufficient to open L-type Ca channels and mediate Ca2+ influx. Herein is described the initiation of RVD in UMR-106.

c-Src is required for stimulation of gelsolin-associated phosphatidylinositol 3-kinase.

We have shown that osteopontin binding to integrin alphav beta3 in osteoclasts stimulates gelsolin-associated phosphatidylinositol (PtdIns) 3-hydroxyl kinase (PI 3-kinase), leading to increased levels of gelsolin-bound PtdIns 3,4-P2, PtdIns 4,5-P2, and PtdIns 3, 4,5-P3, uncapping of barbed end actin, and actin filament formation. Inhibition of PI 3-kinase activity by wortmannin blocks osteopontin stimulation of actin filament formation, suggesting that activation of gelsolin-associated PI 3-kinase is an important pathway in cytoskeletal regulation. To study the mechanism of gelsolin-associated PI 3-kinase activation, we analyzed anti-gelsolin immunoprecipitates for the association of protein kinases.

Regulation of sodium-dependent phosphate transport in osteoclasts.

Osteoclasts are the primary cells responsible for bone resorption. They are exposed to high ambient concentrations of inorganic phosphate (Pi) during the process of bone resorption and they possess specific Pi-transport system(s) capable of taking up Pi released by bone resorption. By immunochemical studies and PCR, we confirmed previous studies suggesting the presence of an Na-dependent Pi transporter related to the renal tubular "NaPi" proteins in the osteoclast.

Engagement of the osteoclast integrin alpha v beta 3 by osteopontin stimulates phosphatidylinositol 3-hydroxyl kinase activity.

Osteoclast adhesion via integrin alpha v beta 3 to the bone matrix protein osteopontin (OPN) results in stimulation of bone resorption. We characterized an immediate signaling event that takes place upon osteoclast interaction with OPN. OPN binding to alpha v beta 3 results in the rapid production of the phosphoinositides (PtdInsP), including phosphatidylinositol triphosphate (PtdIns 3,4,5P3).

Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells.

Hypertension is a major complication of rHuEPO therapy in hemodialysis (HD) patients. We have previously reported that patients receiving rHuEPO intravenously (i.v.

Characterization of phospholipase C activity of the plasma membrane and cytosol of an osteoblast-like cell line.

The properties of phospholipase C (PL-C) in the plasma membranes (PM) and the cytosol of osteoblast-like osteosarcoma cells, UMR-106, were analyzed to see if separate enzymes or similar enzymes were involved in signalling, transduction, and arachidonate release. The cytosolic PL-C displayed substrate affinities in the order of phosphatidylinositol (PI) greater than phosphatidylinositol-4-phosphate (PIP) or phosphatidylinoisitol-4, 5-bisphosphate (PIP2). Hydrolysis of PI, PIP, and PIP2 by cytosolic PL-C was not affected by GTP or GTP gamma S and other nucleotides.

Effect of 1,25-dihydroxyvitamin D3 on phospholipid composition of rat renal brush border membrane.

To analyze the effects of vitamin D on renal tubular cell membrane phospholipid metabolism, the effects of vitamin D depletion and repletion on renal brush border membrane (BBM) phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylinositol (PI) were studied. The PC content of BBM from kidneys of rats deprived of vitamin D for 5-6 wk was 33.5 +/- 2.