Response to Acthar Gel in sarcoidosis uveitis: A prospective open label study.

Purpose: To investigate the response to Acthar Gel® in patients with moderate to severe sarcoidosis uveitis.

Methods: This is a prospective open-label study that enrolled patients with moderate to severe sarcoidosis uveitis to receive 80 units daily of Acthar Gel for ten days followed by maintenance treatment with 80 units twice weekly. The primary outcome was the proportion of patients meeting at least one of the following variables 1) improved visual acuity, 2) resolution of intraocular inflammation, 3) ability to taper ocular or oral steroids by at least 50% or 4) reduction of cystoid macular edema, with no worsening of any single measure and no need for additional sarcoidosis therapies at 24 weeks.

A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis.

Background: Tobacco smoking is associated with a reduced risk of developing sarcoidosis, and we previously reported that nicotine normalizes immune responses to environmental antigens in patients with active pulmonary sarcoidosis. The effects of nicotine on the progression of pulmonary sarcoidosis are unknown.

Research Question: Is nicotine treatment well tolerated, and will it improve lung function in patients with active pulmonary sarcoidosis?

Study Design And Methods: With local institutional review board approval, a randomized, double-blind, controlled pilot trial was conducted of daily nicotine transdermal patch treatment (21 mg daily) or placebo patch use for 24 weeks.

Clinical features of sarcoidosis associated pulmonary hypertension: Results of a multi-national registry.

Background: Pulmonary hypertension (PH) is a significant cause of morbidity and mortality in sarcoidosis. We established a multi-national registry of sarcoidosis associated PH (SAPH) patients.

Methods: Sarcoidosis patients with PH confirmed by right heart catheterization (RHC) were studied.

Morphine and breast tumor metastasis: the role of matrix-degrading enzymes.

Opioids including morphine are commonly used in pain management during and after cancer surgery but have been linked to a variety of pro- and anti-tumor effects. In the present study the effect of morphine administration on the localization and growth of breast tumor cells in lungs and the level of extracellular matrix (ECM) proteases were investigated. In a mouse syngeneic model of intravenously inoculated breast cancer cells, morphine administration led to a reduction in the localization and growth of tumors in the lungs and a reduction in circulating matrix metalloproteinase-9 (MMP-9) and urokinase-like plasminogen activator (uPA).

Altered localization of H-Ras in caveolin-1-null cells is palmitoylation-independent.

Caveolin-1 is a palmitoylated protein involved in the formation of plasma membrane subdomains termed caveolae, intracellular cholesterol transport, and assembly and regulation of signaling molecules in caveolae. Caveolin-1 interacts via a consensus binding motif with several signaling proteins, including H-Ras. Ras oncogene products function as molecular switches in several signal transduction pathways regulating cell growth and differentiation.

Caveolin-1 polarization in transmigrating endothelial cells requires binding to intermediate filaments.

Caveolin-1 influences cell migration through multiple signaling pathways. In a previous report, we have shown that caveolin-1 is polarized in three-dimensional migrating endothelial cells (EC), and that caveolin-1 accumulation at the front of transmigrating cells requires the phosphorylatable Tyr(14) residue of caveolin-1. Immuno-electron microscopy further indicated that caveolin-1 was distributed along cytoskeletal structures in the anterior of transmigrating EC [Parat MO, Anand-Apte B, Fox PL (Mol Biol Cell 14:3156-3168, 2003)].

Reassessing the role of phosphocaveolin-1 in cell adhesion and migration.

Although phosphorylation on tyrosine 14 was identified early in the discovery of caveolin-1, the functional significance of this modification still remains elusive. Recent evidence points to a role of caveolin-1 tyrosine 14 phosphorylation in cell adhesion and migration. These results are based on a variety of tools, including a widely used mouse monoclonal anti-phosphocaveolin-1 antibody, which labels, in cultured cells, a protein localized at or near focal adhesions.

Caveolin-1 polarization in migrating endothelial cells is directed by substrate topology not chemoattractant gradient.

Polarization is a hallmark of migrating cells, and an asymmetric distribution of proteins is essential to the migration process. Caveolin-1 is highly polarized in migrating endothelial cells (EC). Several studies have shown caveolin-1 accumulation in the front of migrating EC while others report its accumulation in the EC rear.