Ganglioside GT1b inhibits keratinocyte adhesion and migration on a fibronectin matrix

Highly sialylated gangliosides have been shown to alter cellular adhesion to a fibronectin matrix. The effect of these gangliosides on the adhesion, spreading, and migration of cultured keratinocytes on a fibronectin matrix has not been explored. Ganglioside GT1b significantly prevented attachment of keratinocytes to fibronectin and also detached previously adherent keratinocytes in a concentration-dependent manner without cell toxicity. GT1b did not affect adhesion of keratinocytes to wells coated with laminin, type I or type IV collagen, 804G extracellular matrix, or albumin. GT1b also inhibited keratinocyte migration on fibronectin in a concentration-dependent manner at concentrations as low as 5 nM GT1b, but had no effect on migration of keratinocytes plated on other matrices. GT1b binds to intact fibronectin and to the 120-kD RGDS-containing cell-binding fibronectin fragment, but not to the heparin- or gelatin-binding fragments of fibronectin. Although RGDS competes with GT1b in inhibiting adhesion, GT1b does not diminish binding of keratinocytes to a derivatized RGDS substratum, suggesting that the GT1b effect involves a non-RGDS site in the cell-binding region that modulates RGDS/alpha 5 beta 1 integrin receptor interaction. Through a specific effect on keratinocyte interaction with fibronectin, GT1b may participate in the regulation of cell adhesion and migration on a fibronectin substratum, which are important events during wound healing and the spreading of cutaneous neoplasia.     

Hepatitis G virus infection in hemodialysis patients and the effects of interferon treatment

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.     

Differential modulation of NMDA-stimulated [3H]dopamine release from rat striatum by neuropeptide Y and sigma receptor ligands

Although the identity of the endogenous ligands for sigma (sigma) receptors is unknown, neuropeptide Y (NPY) has been named as a possible candidate for a natural transmitter at these receptors. Using a superfusion system, we compared the effect of NPY on NMDA-stimulated [3H]dopamine release in rat striatum to that of the sigma agonists (+)-pentazocine and BD737. In contrast to (+)-pentazocine- or BD737-mediated inhibition of release, NPY enhanced release. However, the same sigma antagonists (BD1008, DuP734, haloperidol and DTG) that reverse (+)-pentazocine- or BD737-mediated inhibition, as well as a Y receptor antagonist, PYX-1, all reversed the enhancement. PYX-1 also reversed the (+)-pentazocine- and BD737-mediated inhibition of release. Peptide YY (PYY) and [Leu31,Pro34]NPY did not mimic the effect of NPY. NPY13-36 enhanced release to the same extent as NPY but the effect was not reversed by sigma antagonists. Our findings are consistent with the potential role of NPY as an endogenous ligand for a subtype of sigma receptor with characteristics different from Y1, Y2 and Y3 receptors but sensitive to PYX-1.     

A carcinoembryonic antigen polynucleotide vaccine for human clinical use

Congenital cataract, type Volkmann (McKusick no 115665, gene symbol CCV) is an autosomal dominant eye disease. The disease is characterized by a progressive, central and zonular cataract, with opacities both in the embryonic, fetal and juvenile nucleus and around the anterior and posterior Y-suture. We examined blood samples from 91 members of a Danish pedigree comprising 426 members, by using highly informative short tandem repeat polymorphisms and found the closest linkage of the disease gene (CCV) to a (CA)n dinucleotide repeat polymorphism at locus D1S243 (Zmax = 14.04 at theta M = 0.025 theta F = 0.000), at a penetrance of 0.90. Using two additional chromosome 1 markers, we were able to map the CCV gene in the sequence 1pter-(CCV, D1S243)-D1S468-D1S214. The (enolase 1) gene has been mapped to this area; however, a mutation described in this gene did not give eye disease.     

Kinetics of fly ash leaching in strongly alkaline solutions

We have leached fly ash samples from six power stations in potassium hydroxide solutions at a water-to-solid mass ratio of 40 g/g. A wet chemical method was developed which provides for a detailed characterization of the reactivity of fly ash. The leaching process could be divided into three stages. In stage one, reaction progress measured by the relative mass of fly ash reacted (α) was controlled by the rate of glass network dissolution while very little gel formed (α < 0.1). In stage two, more gel (mainly oxides of Fe, Ca, Mg, and Ti) formed on the glass surface, and the rate of glass dissolution was limited by diffusion (0.1 < α < 0.45). In stage three, zeolite crystallized on top of the gel layer, and an aluminosilicate gel formed in situ, while diffusion continued to control reaction progress (α > 0.45). The data were modeled using a modified Jander equation and rate constants were calculated for each process. The rate constants for stage one reflect an intrinsic glass property, chemical durability, which increased linearly with increasing concentration of network formers in the glass phase of a fly ash.