Detection of GNAQ mutations and reduction of cell viability in uveal melanoma cells with functionalized gold nanoparticles.

Background: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Early treatment may improve any chances of preventing metastatic disease, but diagnosis of small UM is challenging. Up to 95 % of all UMs carry somatic mutations in the G-coupled proteins GNAQ and GNA11 promoting anchorage-independent growth and proliferation.

Mutations in GNA11 in uveal melanoma.

Background: Uveal melanoma is the most common intraocular cancer. There are no effective therapies for metastatic disease. Mutations in GNAQ, the gene encoding an alpha subunit of heterotrimeric G proteins, are found in 40% of uveal melanomas.

Serum vascular endothelial growth factor (VEGF) levels correlate with number and location of micrometastases in a murine model of uveal melanoma.

Background: A preliminary animal study was performed to determine if hepatic micrometastases from uveal melanoma secrete vascular endothelial growth factor (VEGF) that is measurable in serum.

Methods: We analysed the serum of a C57Bl/6 mouse model of uveal melanoma (n=10) at days 4, 7, 14 and 21 post-inoculation for VEGF levels. We compared the serum VEGF levels with the number and location of hepatic micrometastases and their respective expression of VEGF mRNA.

Conjunctival lichen planus in a patient with herpes simplex virus keratitis.

Purpose: To report a case of lichen planus in a patient with a history of herpes simplex virus keratitis.

Methods: Case report.

Results: A 60-year-old woman with chronic conjunctivitis and a history of herpes simplex virus keratitis was evaluated for irritation and a plaque on her right upper and lower eyelid palpebral conjunctivae.

Anterior diffuse retinoblastoma: mutational analysis and immunofluorescence staining.

Retinoblastoma is the most common primary intraocular tumor of childhood and may be heritable or occur sporadically. Anterior diffuse retinoblastoma is an uncommon variant that is thought to be sporadic. We describe a child with anterior diffuse retinoblastoma who presented with a pseudohypopyon.

Nephritogenic anti-DNA antibodies regulate gene expression in MRL/lpr mouse glomerular mesangial cells.

Objective: Lupus-associated IgG anti-double-stranded DNA antibodies are thought to be pathogenic in the kidney due to cross-reaction with glomerular antigens, leading subsequently to immune complex formation in situ and complement activation. We undertook this study to determine if pathogenic anti-DNA antibodies may also contribute to renal damage by directly influencing mesangial gene expression.

Methods: Complementary DNA microarray gene profiling was performed in primary mesangial cells (derived from lupus-prone MRL/lpr mice) treated with pathogenic, noncomplexed anti-DNA antibodies.

Inflammatory modulation of PPAR gamma expression and activity.

Nitric oxide (NO) production increases with age in the lupus-prone MRL/lpr mouse, paralleling disease activity. One mechanism for excess NO production in MRL/lpr mice may be a defect in down-regulatory mechanisms of the iNOS pathway. A potential modulator of NO is the nuclear hormone receptor peroxisome proliferation activated receptor gamma (PPARgamma).

A novel PPAR response element in the murine iNOS promoter.

The nuclear hormone receptor peroxisome proliferation activated receptor gamma (PPARgamma) is a modulator of inflammation including down-regulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production. PPARgamma agonists reduce iNOS expression and NO production in a dose-dependent manner in macrophages, mesangial cells and other inflammatory cells. However, the mechanisms involved in the inhibition of iNOS expression by PPARgamma and its agonists are not fully understood.

Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPARgamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide.

Peroxisome proliferation-activated receptor (PPAR)gamma agonists inhibit inducible nitric-oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Because of these effects, synthetic PPARgamma agonists, including thiazolidinediones, are being studied for their impact on inflammatory disease. The anti-inflammatory concentrations of synthetic PPARgamma agonists range from 10 to 50 microM, whereas their binding affinity for PPARgamma is in the nanomolar range.