Metastatic and nonmetastatic models of retinoblastoma.

To generate animal models of retinoblastoma that closely resemble metastatic and nonmetastatic human disease for the purposes of examining tumor biology and developing alternate treatments, human retinoblastoma cell lines were injected into the vitreal cavities of immunodeficient mice. Two reproducible animal models with contrasting biological behaviors analogous to human retinoblastoma have been developed. The Y79 retinoblastoma model demonstrated specific tumor evolution similar to that seen in human invasive and metastatic disease.

Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene.

Irish setter dogs affected with a rod/cone dysplasia (locus designation, rcd1) display markedly elevated levels of retinal cGMP during postnatal development. The photoreceptor degeneration commences approximately 25 days after birth and culminates at about 1 year when the population of rods and cones is depleted. A histone-sensitive retinal cGMP phosphodiesterase (PDE; EC 3.

Affinity purification of the photoreceptor cGMP-gated cation channel.

The cGMP-gated cation channel is a member of a new family of channel proteins that appear to be directly regulated by cyclic nucleotides. A protein with a subunit molecular mass of 78 kDa that exhibits cGMP-gated calcium flux when reconstituted into phospholipid-containing vesicles has been purified using 8-bromo-cGMP-agarose affinity chromatography. This channel activity is sensitive to the inhibitor l-cis-diltiazem.

Expression of the functional cone phototransduction cascade in retinoblastoma.

Retinoblastoma is a malignant intraocular tumor that primarily affects small children. These tumors are primitive neuroectodermal malignancies, however some of them show morphologic evidence of differentiation into photoreceptors. Phototransduction cascades are a series of biochemical reactions that convert a photon of light into a neural impulse in rods and cones.

Induction of a calcium/calmodulin-dependent phosphodiesterase during phytohemagglutinin-stimulated lymphocyte mitogenesis.

A calmodulin (CaM)-dependent phosphodiesterase activity that hydrolyzes both cGMP and cAMP was observed in anion exchange high performance liquid chromatography (HPLC) profiles from phytohemagglutinin-stimulated mononuclear cells but not in profiles from unstimulated cells. A single polypeptide was detected by an antibody to the calmodulin-dependent phosphodiesterases on a Western blot of homogenates of stimulated mononuclear cells. The phosphodiesterase activity was immunoadsorbed in a calcium-dependent manner by an antibody to calmodulin but not by an antibody to the 61-kDa bovine brain phosphodiesterase.