The results of cetuximab treatment of a patient with multiple pretreated, irinotecan resistant metastatic colorectal cancer

Aim: The case of a patient with heavily pretreated, irinotecan-resistant, metastatic colorectal cancer is presented by the authors, and they would like to point to the effectiveness of a new therapeutic option, cetuximab treatment. Additionally, they would like to call attention to the need of performing EGFR determination from all of the biopsy samples (primary tumor, lymph nodes and metastases) to start the treatment. A weak EGFR-positivity of the primary tumor in fact does not mean the contraindication of cetuximab treatment, since the metastases, which are usually treated, could be strongly positive. The therapeutic answer could be excellent in this case, as it occurred in our case.     

An enzyme-amplified diffraction-based immunoassay

We have previously shown that a gold-conjugated secondary label can be used to reduce the limit of detection in a diffraction-based assay by more than 40-fold. We now show that by using a combination of a peroxidase-conjugated secondary label and a precipitating substrate the limit of detection in a diffraction-based assay can be reduced by more than 1000-fold. The response to secondary enhancement was linear for concentrations from 50 to 2000 pg/mL of antidigoxin.     

Chicken retinas contain a retinoid isomerase activity that catalyzes the direct conversion of all-trans-retinol to 11-cis-retinol

Vertebrate retinas contain two types of light-detecting cells. Rods subserve vision in dim light, while cones provide color vision in bright light. Both contain light-sensitive proteins called opsins. The light-absorbing chromophore in most opsins is 11-cis-retinaldehyde, which is isomerized to all-trans-retinaldehyde by absorption of a photon. Restoration of light sensitivity requires chemical re-isomerization of retinaldehyde by an enzymatic pathway called the visual cycle in the retinal pigment epithelium. The isomerase in this pathway uses all-trans-retinyl esters synthesized by lecithin retinol acyl transferase (LRAT) as the substrate. Several lines of evidence suggest that cone opsins regenerate by a different mechanism. Here we demonstrate the existence of two catalytic activities in chicken retinas. The first is an isomerase activity that effects interconversion of all-trans-retinol and 11-cis-retinol. The second is an ester synthase that effects palmitoyl coenzyme A-dependent synthesis of all-trans- and 11-cis-retinyl esters. Kinetic analysis of these two activities suggests that they act in concert to drive the formation of 11-cis-retinoids in chicken retinas. These activities may be part of a new visual cycle for the regeneration of chromophores in cones.     

Blidingia minima var. stolonifera var. nov. (Ulvales, Chlorophyta) from British Columbia: systematics, life history and morphogenesis

Blidingia minima var. stolonifera var. nov. is described from Vancouver, British Columbia. In previous literature this variety may have been confused with B. chadefaudii and B. minima var. minima. The new variety is part of the B. minima species complex in which spores germinate by evacuating the original spore and forming a germ tube. B. minima var. stolonifera is characterized by the development of marginal filaments on the basal disc that have one to five colourless cells and terminate in a cell from which a new disc grows. Colourless cells are devoid of chloroplasts and nuclei, and contain only small remnants of cytoplasm. The runner system is considered a mechanism of vegetative growth and propagation that enables a disc to cover a large amount of substratum before producing erect, unbranched thalli. In field and in culture, B. minima var. stolonifera typically reproduces by means of quadriflagellate zoospores; however, three plants from Vancouver formed biflagellate spores. These germinated poorly and developed into highly irregular, branched thalli.     

Rpe65 is a retinyl ester binding protein that presents insoluble substrate to the isomerase in retinal pigment epithelial cells

Photon capture by a rhodopsin pigment molecule induces 11-cis to all-trans isomerization of its retinaldehyde chromophore. To restore light sensitivity, the all-trans-retinaldehyde must be chemically re-isomerized by an enzyme pathway called the visual cycle. Rpe65, an abundant protein in retinal pigment epithelial (RPE) cells and a homolog of beta-carotene dioxygenase, appears to play a role in this pathway. Rpe65-/- knockout mice massively accumulate all-trans-retinyl esters but lack 11-cis-retinoids and rhodopsin visual pigment in their retinas. Mutations in the human RPE65 gene cause a severe recessive blinding disease called Leber's congenital amaurosis. The function of Rpe65, however, is unknown. Here we show that Rpe65 specifically binds all-trans-retinyl palmitate but not 11-cis-retinyl palmitate by a spectral-shift assay, by co-elution during gel filtration, and by co-immunoprecipitation. Using a novel fluorescent resonance energy transfer (FRET) binding assay in liposomes, we demonstrate that Rpe65 extracts all-trans-retinyl esters from phospholipid membranes. Assays of isomerase activity reveal that Rpe65 strongly stimulates the enzymatic conversion of all-trans-retinyl palmitate to 11-cis-retinol in microsomes from bovine RPE cells. Moreover, we show that addition of Rpe65 to membranes from rpe65-/- mice, which possess no detectable isomerase activity, restores isomerase activity to wild-type levels. Rpe65 by itself, however, has no intrinsic isomerase activity. These observations suggest that Rpe65 presents retinyl esters as substrate to the isomerase for synthesis of visual chromophore. This proposed function explains the phenotype in mice and humans lacking Rpe65.